Search

Aims Giant lamellar bodies (GLBs) are rare pulmonary inclusions, most frequently described in sclerosing haemangiomas. Following a recent report of their presence in a case of pulmonary lymphoma of MALT origin, our aims were to determine their frequency in pulmonary lymphoproliferative disorders, examine their structure and investigate their aetiology further. Methods and results We reviewed a series of 29 pulmonary lymphomas (23 low-grade, six high-grade) and 18 cases of reactive pulmonary lymphoid hyperplasia. Five of 23 (22%) low-grade lymphomas contained GLBs, 4/4 of which stained for surfactant apoprotein A but not for surfactant apoprotein B. No GLBs were seen in 18 cases of reactive pulmonary lymphoid hyperplasia or six high-grade primary pulmonary lymphomas. Ultrastructural examination revealed concentrically arranged extracellular material forming roughly spherical structures up to 25 μm in diameter. The GLBs were often surrounded by foamy cells and cholesterol clefts, supporting an origin, at least in part, from products of cell breakdown and surfactant degradation. Conclusion These findings support the idea that the presence of lamellar bodies is in part due to stasis of products arising from degradation of surfactant, in association with certain types of chronic pulmonary pathology. Given their absence in reactive pulmonary lymphoid hyperplasia, the presence of GLBs as an epiphenomenon in a pulmonary lymphoid infiltrate should warrant careful investigation with regard to the diagnosis of low-grade MALT lymphoma. [ABSTRACT FROM AUTHOR]

Objective: There is evidence indicating that the risk of respiratory distress syndrome is reduced in preterm neonates exposed to intra-amniotic infection and/or inflammation. We hypothesised that foetal lung maturation promoted by intra-amniotic infection and/or inflammation results in elevated lamellar body count (LBC) in amniotic fluid (AF). This study aimed to determine the relationship between LBC in AF and intra-amniotic infection and/or inflammation in patients with threatened preterm birth., Study Design: This was a retrospective cohort study of patients with threatened preterm birth. A total of 104 consecutive pregnant women underwent amniocentesis in the early preterm period [gestational age < 34 weeks] to evaluate intra-amniotic infection and/or inflammation and foetal lung maturity. Intra-amniotic infection was confirmed by positive AF culture results for aerobic/anaerobic bacteria, fungi, and genital mycoplasma. Intra-amniotic inflammation was defined as a positive AF matrix metalloproteinase-8 rapid test. Outcomes of the study population were compared according to LBC in AF using a cut-off of 15,000/mm 3 ., Results: The rates of elevated LBC and intra-amniotic infection and/or inflammation were 23% (24/104) and 52% (54/104), respectively. The median LBC was significantly higher in patients with intra-amniotic infection and/or inflammation than in those without [median LBC, 9,000/mm 3 (interquartile range, IQR: 3,000-39,000) vs. 3,000/mm 3 (IQR: 2,750-5,000), p < 0.001]. Intra-amniotic infection and/or inflammation was observed in 96% (23/24) of patients with elevated LBC and 39% (31/80) of patients without elevated LBC (p < 0.001). On multivariable analysis, the presence of intra-amniotic infection and/or inflammation was significantly associated with elevated LBC with an odds ratio (OR) of 66.0 [95% confidence interval (CI) 6.6-664.4, p < 0.001], even after accounting for gestational age at amniocentesis being a significantly related factor for predicting elevated LBC with an OR of 1.5 (95% CI 1.1-2.0, p = 0.004)., Conclusion: LBC elevation was independently associated with the presence of intra-amniotic infection and/or inflammation in women with early threatened preterm birth (gestational age < 34 weeks). This finding may support the view that an intra-amniotic inflammatory response promotes foetal lung maturation that can be detected by elevated LBC in AF., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The lamellar body (LB), a concentric structure loaded with surfactant proteins and phospholipids, is an organelle specific to type 2 alveolar epithelial cells (AT2). However, the origin of LBs has not been fully elucidated. We have previously reported that autophagy regulates Weibel-Palade bodies (WPBs) formation, and here we demonstrated that autophagy is involved in LB maturation, another lysosome-related organelle. We found that during development, LBs were transformed from autophagic vacuoles containing cytoplasmic contents such as glycogen. Fusion between LBs and autophagosomes was observed in wild-type neonate mice. Moreover, the markers of autophagic activity, microtubule-associated protein 1 light chain 3B (LC3B), largely co-localized on the limiting membrane of the LB. Both autophagy-related gene 7 ( Atg7 ) global knockout and conditional Atg7 knockdown in AT2 cells in mice led to defects in LB maturation and surfactant protein B production. Additionally, changes in autophagic activity altered LB formation and surfactant protein B production. Taken together, these results suggest that autophagy plays a critical role in the regulation of LB formation during development and the maintenance of LB homeostasis during adulthood., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Structures identified as annulate lamellae, lamellar bodies and subsurface cisternae were found in neurons of the hyperstriatum accessorium of the avian forebrain. Annulate lamellar arrays with up to six lamellae were present in the larger somata. The lamellae were made up of fused smooth-surfaced cisternae forming pores or annuli and were surrounded by a dense filamentous to granular material. Stacks of nonfenestrated, parallel, regularly spaced cisternae, designated as lamellar bodies, also appeared in the cytoplasm. When flattened they were reminiscent of the electron dense subsurface cisternae. Continuity could be demonstrated between peripherally located subsurface cisternae and lamellar bodies. The dense filamentous to finely granular substance was also located between these structures. Annulate lamellae, lamellar bodies and subsurface cisternae were always observed in conjunction with the rough endoplasmic reticulum. The functional significance of these structural associations is considered. [ABSTRACT FROM AUTHOR]

The columnar epithelial cells of the gas gland in the swimbladder of the toadfish, Opsanus tau L., contain lamellar bodies that resemble the lamellar bodies found in epithelial cells of vertebrate lungs. Cytochemical assays indicate that swimbladder lamellar bodies are soluble in chloroform-methanol solution, react with tricomplex flocculation solution (indicating a phospholipid component), exhibit a positive reaction for cholesterol when exposed to digitonin, and contain acid phosphatase. The anterior chamber of the toadfish swimbladder is lined by an extracellular layer. Digitonin-cholesterol crystals are found in this layer when the swimbladder is treated with digitonin. A ruthenium red positive layer is also present in the anterior chamber of the toadfish swimbladder. The structure and cytochemistry of swimbladder lamellar bodies are compared with those of vertebrate lung lamellar bodies. Similarities between the extracellular layer in the swimbladder and the extracellular layer in lungs are also noted. [ABSTRACT FROM AUTHOR]

Lamellar bodies in first cleavage Xenopus laevis embryos have been examined with the electron microscope. Based on the arrangement and relative thickness of the lamellae, three types of lamellar bodies have been identified. In the first type, a band of two to ten lamellae (spacing about 3.5 nm) was intertwined at random. This type of lamellar body was seen closely associated with the concave or the forming face of the Golgi body and may have been derived from this organelle. The frequent association of these lamellar bodies with the growing cleavage furrow may suggest a transfer of materials from the Golgi body to the furrow through the lamellar bodies or their precursors. In the second type, typical myelin-like figures with a repeating distance of about 10 nm were located close to the furrow tip. In the third type, membrane whorls containing tetrads of lamellae (approximately 16 nm thickness) were seen associated with lipid droplets. If the lamellar bodies observed in this study were formed during fixation then the appearance of three different types after the same fixation procedure would indicate the presence of a similar number of pools of precursor materials which differ in their chemical composition and distribution in the embryo. [ABSTRACT FROM AUTHOR]

Biochemical and ultrastructural analysis of epidermis from the porpoise, Phocena phocena, revealed certain similarities and differences between cetaceans and terrestrial mammals. The predominant cell of cetacean epidermis, not found in normal terrestrial mammals, is a lipoker-atinocyte, which elaborates not only keratin filaments, but also two types of lipid organelles: first, lamellar bodies, morphologically identical to those of terrestrial mammals, are elaborated in great abundance in all suprabasal epidermal layers, forming intercellular lipid bilayers in the stratum corneum interstices: and second, non-membrane-bounded droplets appear and persist in all epidermal layers. Although the porpoise lipokeratinocyte morpologically resembles the sebokeratocyte of avians in certain respects, nonmembrane-bounded lipid droplets are not released into the intercorneocyte space as they are in avian stratum corneum. Whereas phospholipid/neutral lipid gradients are similar in porpoise and terrestrial mammals, PAS-positive glycoconjugates, specifically glycosphingolipids, are retained in porpoise stratum corneum, but lost from these layers in terrestrials. The novel, non-polar acylglucosyl-ceramides, which also are lost during cornification in terrestrial mammals, are retained in porpoise stratum corneum. The lipid components of porpoise lipokeratinocytes appear to subserve not only barrier function in a hypertonic milieu, but also underlie the unique buoyancy, streamlining, insulatory, and caloric properties exhibited as adaptations to the cetacean habitat. [ABSTRACT FROM AUTHOR]

The fine structure of subsurface cisternae and lamellar bodies in the outer hair cells of the guinea-pig organ of Corti was studied with thin sections and freeze-fracture replicas. Subsurface cisternae in the outer hair cells consist of multilayers along the lateral plasma membrane of the cell. The outermost layer is a flattened cistern in the upper part of the supranuclear region, but comprises a series of tubules in the lower part. Deeper layers are fenesrated cisternae in which disc-like areas are found in the upper part of the supranuclear region. Lamellar bodies consist of concentric layers of fenestrated cisternae and are located in the apical cytoplasm beneath the cuticular plate. They are continuous with the subsurface cisternae. In the supranuclear cytoplasm, bulges of the subsurface cisternae and the lamellar bodies are found. Dilated cisternae are also present. Some dilated cisternae contain many small vesicles, which display acid phosphatase activity. The dilated cisternae are considered as forms of the bulges undergoing transformation into multivesicular bodies. The possible role of the lamellar bodies, and the origin and fate of the subsurface cisternae are discussed. [ABSTRACT FROM AUTHOR]

Subsurface cisterns (SSC's) and less frequent lamellar bodies (LB's) were identified in the granule cells of the guinea-pig fascia dentata. Both structures, composed of flattened or collapsed agranular cisterns, are continuous with the regular rough endoplasmic reticulum and occasionally connected with each other forming LB-SSC complexes. The SSC's are apposed to glia, synaptic boutons, and nerve cell processes as well as to neighboring granule cells appearing here singly and in confronting pairs. The quantitative analysis of the various cisternal appositions compared to the distribution of the tissue components on the granule cell soma shows that the overwhelming majority of SSC's are related to glial cells. [ABSTRACT FROM AUTHOR]

Lung tissue expiants from mid-trimester human abortuses were maintained for 8 days in organ culture in medium with or without serum. Before the start of culture the cells lining the pre-alveolar ducts were undifferentiated and contained no lamellar bodies, the intracellular organelle that contains surfactant. After 4 days in organ culture, the epithelium lining the pre-alveolar ducts was composed of differentiated type II cells containing numerous lamellar bodies. During the 8-day culture period there was increased incorporation of [H]choline into phosphatidylcholine and disaturated phosphatidylcholine. In addition, the specific activity of phosphatidate phosphohydrolase, a regulatory enzyme in lung phospholipid synthesis, increased 4-fold during the culture period. Lamellar bodies isolated by differential centrifugation from expiants maintained in culture for 7 days had the characteristic ultrastructure described for this organelle. Lamellar bodies were isolated from expiants which had been incubated with [C]glycerol. When the glycerophospholipid composition of lamellar bodies was analyzed it was found that the majority of the radiolabeled glycerol (74%) was incorporated into phosphatidylcholine and into the anionic phospholipids, phosphatidylglycerol (5%) and phosphatidylinositol (6%). Thus, human fetal lung expiants maintained in organ culture contain differentiated type II cells which synthesize surfactant characteristic of human fetal lung at 36 to 38 weeks of gestation. [ABSTRACT FROM AUTHOR]

Previous studies have shown that synovial surfactant could have beneficial roles in the joint, especially as a very effective boundary lubricant capable of high load bearing. This study is aimed at further characterization and identification of the source. Known to be an important minor component of pulmonary surfactant, proteolipid has now been detected in appreciable quantities in bovine synovial fluid and bound to the articular surface. Using standard procedures to separate it from the major component [surface-active phospholipid (SAPL)] by column chromatography, proteolipid :phospholipid ratios were found to be comparable to those in the lung or in lamellar bodies (LBs). LBs are the unequivocal source of surfactant in the lung and we have confirmed an earlier study demonstrating their presence in Type B synoviocytes. Using a fixation procedure specifically designed to preserve the graphite-like structure of SAPL deposited as oligolamellar layers, or coiled as lamellar bodies, we were able to demonstrate these structures in equine joints adjacent to the Golgj apparatus associated with the secretory mechanism of the cell. These results indicate that proteolipid could be facilitating the deposition of the graphite-like surface lining of SAPL providing efficient boundary lubrication just as it promotes surfactant adsorption in the lung and in the formation of myelin. Any deficiency in synovial surfactant, compromising its roles in the joint, is discussed in relation to osteoarthritis and the possible administration of exogenous SAPL to the degenerating joint. [ABSTRACT FROM PUBLISHER]

The intra- and extracellular distribution and relative density of lamellar bodies (LBs) were determined by electron microscopy in synovial biopsies from 20 non-rheumatoid arthritis (RA) patients. LBs were found on the synovial surface, in Lntimal cells, throughout intimal matrix, in blood vessel walls, in endothelial cytoplasm and within vascular lumena. Lamellar profiles were observed in type B synoviocytes within rough cndopLasmic reticulum (RER), in association with the Golgi apparatus, and embedded in electron dense matrix (projection cores) in multivesicular bodies. Exocytotic release of mature LBs into intimal matrix was observed. In type A synoviocytes the outer lamellae of LBs were frequently found in contiguity with the limiting membrane of lysosomes. An investigation of the ultrastructural features of LB formation in cultured type B synoviocytes (from 3 non-RA patients) gave results similar to those obtained in biopsies. These studies provide ultrastructural evidence of synoviocyte activity in secreting and degrading phospholipid lubricant in a sophisticated system whose function and pathological derangements are largely unknown. [ABSTRACT FROM PUBLISHER]

Intracytoplasmic lamellar organelles identical in ultrastructure to surfactant-containing lamellar bodies found in type II pneumocytes, have been demonstrated in other tissues, in synoviocytes and mesothelial cells, in a distribution pattern which reflects the systemic expression of rheumatoid disease. Antibodies raised against surfactant protein A (SP-A), exhibit a ranking of tissue reactivity in area, intensity and density of cells which also parallels the frequency and degree of pathological involvement characteristic of rheumatoid disease, showing in ascending order of immunopositivity, lachrymal and salivary epithelia, pulmonary parenchyma, mesothelium and synoviocytes. Maximal tissue reactivity to anti-SP-A antibodies was found in the synovium of 55 rheumatoid patients exhibiting classical histopathological appearances of RA, in a pattern of immunostaining identical to that obtained with ML30, an antibody to mycobacterial heat shock protein 65kDa which, in turn, cross-reacted with SP-A in dot blot testing. [ABSTRACT FROM PUBLISHER]

The fetal respiratory distress syndrome is due, in part, to the presence of abundant pre-type II alveolar epithelial cells that have not yet differentiated into mature type II cells. Studies of this syndrome have been limited somewhat by the lack of an adequate in vitro model. In the present study we immortalized pre-type II cells by infecting primary isolates obtained from fetal rat lung with a retroviral construct expressing the adenoviral 12S E1A gene product. The immortalized pre-type II cells retained many of the ultrastructural features typical of pre-type II cells in primary culture, most notably lamellar bodies were not detected and the cells contained abundant stores of glycogen, expressed cytokeratin filaments, and bound the lectin Maclura pomifera. Karyotyping revealed that the cells are diploid. Growth studies demonstrate log phase growth in the presence of serum with a markedly decreased growth rate shortly after the cells reach confluence. Exposure of the immortalized pre-type II cells to hydrocortisone and dibutryl cAMP resulted in the induction of lamellar bodylike organelles; however, these cells did not secrete surfactant or express surfactant protein A. These cells may serve as useful models for some in vitro studies of fetal type II cell maturation or the fetal respiratory distress syndrome, or both. [ABSTRACT FROM AUTHOR]

Amiodarone HCl (AD) is a very effective antiarrhythmic drug, but its use is often associated with serious pulmonary complications. It is shown to induce lung phospholipidosis. Nevertheless, the effects of this drug on pulmonary surfactant which is composed of about 75% phospholipids and which prevents alveolar collapse is not known. Therefore, we have examined the effect of AD on the intra- and extracellular surfactant pools and on the levels of phosphatidylcholine (PC), the primary constituent of pulmonary surfactant. Male Wistar rats were fed AD (175 mg/kg) by oral gavage for three weeks. At the end of the experimental period, the rats were killed, the lungs removed and perfused, and surfactant isolated. Some lungs were prepared for ultrastructural examination. Phospholipid was assayed in the intra- and extracellular surfactant. Amiodarone produced a significant increase in both the intra- and extracellular sufactant phospholipid along with an appreciable change in the phospholipid profile. Also, the drug seemed to increase the number of lamellar inclusions in the surfactant producing type II alveolar cells. These data suggest that administration of AD leads to an increase in the lung surfactant phospholipid levels and lamellar bodies in alveolar type II cells. [ABSTRACT FROM AUTHOR]

The behavior of fibroblast-populated collagen lattices under mechanical stress was studied. Lattice retraction was blocked to allow the application of mechanical stress by contraction of the fibroblasts against the fixed ends of the lattice. The forces were modulated by varying the collagen/fibroblast ratio and the amount of collagen fibrils produced, by which the forces were transmitted. Transmission electron microscopy showed several disturbances of fibroblast ultrastructure, with empty and full vacuoles, lamellar bodies and signs of cytolysis. It is suggested that the morphological alterations in the fibroblasts may constitute a feedback reaction to the mechanical stress. [ABSTRACT FROM AUTHOR]

Birds in the genus Pitohui and Ifrita carry potent neurotoxins that are most abundant in skin and feathers. It was unknown precisely how or where in the skin these chemicals are stored. Here, we report high-resolution electron microscopy using Os O4 staining to visualize the location of alkaloids. Our images suggest that toxic alkaloids accumulate in multigranular bodies of epidermal cells and are likely secreted as part of the avian epidermal barrier, where they are made available for chemical defense. [ABSTRACT FROM AUTHOR]

Structures identified as subsurface cisterns (SSC's) and lamellar bodies (LB's) have been observed in the neurons, but not in the glial cells, of the rat and cat substantia nigra. The SSC's are most often opposite what appears to be glial cells, but they are also subsynaptic in position. A single, large (0.4-1.5 μ), unfenestrated, usually flattened cistern closely underlies the inner aspect of the plasma membrane of the perikaryon and proximal parts of the neuronal processes at a regular interval ranging about 100-130 Å. They are sheet-like or discoid in configuration and consists of a pentalaminar structure which usually widens at its lateral edges where its membranes are continuous with each other or with rough ER profiles. Filaments, about 70 Å thick, bridge the cleft between the SSC and the overlying plasmalemma. One or more ER cisterns devoid of ribosomes except on their outermost membrane may be stacked up parallel to an SSC and immediately subjecent to it. A dense filamentous network intervenes between the SSC and its closely applied ER cisterns. At higher magnification, it is seen to consist of a finely textured material which is apparently composed of loosely packed tiny particles. These constituent subunits in turn may represent transverse sections of very fine filaments rather than granules. A mitochondrion frequently occurs in the immediate vicinity of an SSC and may be closely applied to its deep surface. Stacks of unfenestrated, parallel, regularly spaced (about 300-400 Å) cisterns, designated lamellar bodies, appear deeper in the karyoplasm. They are most often flattened and appear as pentalaminar structures. These cisterns, as well as the dense filamentous network intervening between them, are structurally similar to those closely applied to SSC's. They are also devoid of ribosomes except on their outermost surfaces. Whorls of similar cisterns are also occasionally observed. Another particular feature of the rough ER consists of the close apposition of two cisterns without any ribosome attached to the inner membranes of the latter structure. It evokes a simplified type of LB's. It is of particular interest to point out that all these cisterns, i.e. the SSC's, their closely applied cistern(s) and those forming the LB's, are connected to the RER membranes, so that a continuous channel occurs between the nuclear membrane and the SSC which closely underlies the plasma membrane. Our observations show that the SSC's and the LB's are structurally related forms of the ER. A parallel may be drawn between the SSC and the lateral element(s) of a dyad (triad). The structural complex consisting of an SSC, the overlying plasmalemma and the cross-bridges linking them, indeed, bears some resemblance to a dyad. It is suggested that membranes which are closely applied may interact, resulting in alterations in their respective properties. These patches of the neuronal plasma membrane associated with SSC's may, therefore, have special properties because of this relationship, resulting in a non-uniform spread of an action potential on the neuronal surface. The possible significance of SSC's in relation to neuronal electrophysiology, as well as of the latter structures and LB's in relation to cell metabolism, is to be discussed. [ABSTRACT FROM AUTHOR]

Lamellar bodies are described in the non-ciliated epithelial bronchiolar cells of the normal mouse lung. They are constituted of smooth concentric membranes, with a cytoplasmic center. They are related to mitochondria. They seem to belong to smooth endoplasmic reticulum. An origin from Golgi elements is discussed. [ABSTRACT FROM AUTHOR]

With the rapid increase in application of disinfectants worldwide as a method to block the spread of coronavirus, many new products are being introduced into the market without thorough verification of their impacts on human health and the environment. In the present study, we aimed to propose a screening marker for materials that can induce fibrotic lung disease using disinfectants, which had been demonstrated as causative materials of chronic inflammation and interstitial fibrosis. We first calculated the corresponding LC 50 level based on results from cell viability test and exposed the LC 50 level of disinfectants to human bronchial epithelial cells for 24 h. Formation of lamellar body-like structures, cleavage of the nuclear matrix, structural damage of mitochondria were found in the cytosol of the treated cells. We also dosed disinfectants by pharyngeal aspiration to mice to determine the LD0 level. The mice were sacrificed on Day 14 after a single dosing, and lamellar body-like structures were observed in the lung tissue of mice. Herein, we hypothesize that DNA damage and metabolic disturbance may play central roles in disinfectant-induced adverse health effects. Additionally, we propose that formation of lamellar bodies can be a screening marker for interstitial fibrosis. [Display omitted] • The use of disinfectants is rapidly increasing to block spreading of coronavirus. • We identified a screening marker for disinfectants that can induce fibrotic lesions. • Lamellar body-like structures were notably formed in the disinfectant-treated cells. • Cleavage of the nuclear matrix and damage of mitochondrial structures were observed. • Disinfectants should be introduced into the market under thorough verification on the safety. [ABSTRACT FROM AUTHOR]

Inhalation is the main route of nanoparticles (NP) exposure during manufacturing. Although many mechanisms of toxicity have been described, the interaction of NP with relevant pneumocytes organelles is not widely understood. Considering that the physicochemical properties of NP influence their toxicological responses, the objective of this study was to evaluate whether exposure to different NP, crystalline Fe 3 O 4 NP and amorphous SiO 2 NP could alter pneumocytes organelles in alveolar epithelial cells. To achieve this goal, cell viability, ultrastructural changes, lysosomal damage, mitochondrial membrane potential (MMP), lipid droplets (LD) formation and cytokines production were evaluated by MTT, electron microscopy, lysotracker red staining, JC-1, Oil Red staining and Milliplex® assay respectively. Both NP were observed within lamellar bodies (LB), lysosomes, and cytoplasm causing morphological changes. Exposure to SiO 2 NP at 6 h induced lysosomal activation, but not Fe 3 O 4 NP. MMP decreased and LD increased at the highest concentrations after both NP exposure. Pro-inflammatory cytokines were released only after SiO 2 NP exposure at 48 h. These results indicate that SiO 2 NP have a greater impact than Fe 3 O 4 NP on organelles responsible for energy, secretion, degradation and metabolism in pneumocytes leading to the development of respiratory disorders or the exacerbation of preexisting conditions. Therefore, the established biocompatibility for amorphous NP has to be reconsidered. Unlabelled Image • The endosome-lysosome system is the cellular target of SiO 2 NP exposure. • Mitochondria and cellular metabolism are impaired after Fe 3 O 4 NP and SiO 2 NP. • There is an interaction between NP-loaded vesicles and mitochondria. • SiO 2 NP induced more intense cellular stress in pneumocytes organelles than Fe 3 O 4 NP. [ABSTRACT FROM AUTHOR]

Background: The lamellar body count (LBC) plays a crucial role in fetal lung maturity testing. Lamellar bodies are often counted in the platelet channel of routine hematology analyzers, resulting in a rapid and inexpensive assay for fetal lung maturity. Recently, significant imprecision was noted during LBC validation on the Beckman Coulter Unicel DxH 800. Methods: The results of two Beckman Coulter Unicel DxH 800 instruments were compared to those of a Coulter LH 750 and Coulter LH 500. Three pools of amniotic fluid, commercial quality control materials, and proficiency test specimens were analyzed on all four instruments. Fifty patient specimens were also analyzed using the Coulter LH 500 and the Unicel DxH 800. Results: The mean values and precision obtained from commercial quality control materials and proficiency test samples were comparable on all four instruments. However, many erroneously low LBC results were produced from amniotic fluid pools using both DxH 800 instruments. The erroneous values were approximately 50% lower than respective target values, occurred randomly, and affected the low, medium, and high LBC results. Inter-assay precision of the three pools ranged from 24.7 to 39.0 CV% on the DxH 800 instruments. Conclusions: The source of LBC errors likely involves the exclusion of smaller lamellar bodies from the counts. The DxH 800 combines new data fusion technology and mathematical algorithms to produce increased accuracy and flagging efficiency. Laboratorians should be aware that the improved specificity of the DxH 800 may preclude its use for this laboratory-developed test. [ABSTRACT FROM AUTHOR]

Extensive pulmonary fibrosis is a rare occurrence in pulmonary alveolar proteinosis. We report 2 cases that have interesting implications. A female patient was diagnosed with autoimmune pulmonary alveolar proteinosis that evolved over 7 years into diffuse fibrosis. In a male patient with diffuse fibrosis we incidentally detected electron microscopic features of alveolar surfactant accumulation and positive autoantibodies to granulocyte-macrophage colony stimulating factor. In the male patient we speculated that the pulmonary fibrosis might have been preceded by an asymptomatic phase of autoimmune pulmonary alveolar proteinosis, and that we should investigate the involvement of surfactant dysfunction in the pathogenesis of fibrotic lung disease. [ABSTRACT FROM AUTHOR]

Objective: We aimed to find a single numeric cut-off point in order to predict respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN), through quantification of the lamellar bodies (LBs) count. Materials and methods: Two hundred and twenty-seven single pregnancies delivered within 48 h from amniocentesis in a III level university hospital in a period between 1996 and 2007. LBs counts were determined by amniotic fluid (AF) sampling and after centrifugation in a commercially available Coulter counter. LBs counts were performed in order to predict the risk of neonatal RDS and also evaluated against the risk of TTN by means of the most suitable receiver operator characteristic (ROC) curve in order to predict RDS and TTN. Results: The best LBs cut-off to significantly predict TTN was ≤35,000/μL [sensitivity 86%, specificity 75%, positive predictive value (PPV) 22% and negative predictive value (NPV) at 96%]. An LBs count ≤32,000/μL was the best compromise between sensitivity and specificity in predicting RDS or TTN [sensitivity 86%, specificity 83%, PPV 37% and NPV at 97%]. Conclusions: The quantification of LBs is a reliable method, simple to execute, useful in predicting RDS, and may be useful in evaluating suspicion of TTN. [ABSTRACT FROM AUTHOR]

The skin presents a mechanical, as well as an immunological barrier to infection, and displays considerable innate immune capacity. Recently, cultured human keratinocytes were described to produce and export a microbicidal peptide human β-defensin 2 (HBD-2). Immunogold was used to label ultrathin cryosections of stimulated, cultured human epidermis. HBD-2 was found to be stored in the lamellar bodies (LBs) of the stimulated keratinocytes of the spinous layer of the epidermis. HBD-2 was also found in the intercellular space. These findings suggest that HBD-2 is released with the contents of the LBs. Along with other investigations, our findings indicate that the lipid “permeability” barrier of the skin contains antimicrobial substances. [Copyright &y& Elsevier]

This study aimed to investigate the mechanism of propofol (PR) pretreatment inducing high heme oxygenase-1 (HO-1) expression to protect alveolar type II epithelial cells (AEC-II) in rats with acute lung injury (ALI) induced by oleic acid (OA). In this study, 32 male Sprague-Dawley rats (250 - 300 g) were randomly divided into four groups (n = 8 in each group) as follows: group C (the normal control group), the OA group (the oleic acid injury control group), the OA + PR group (the PR pretreatment group), and the OA + IX group (the zinc porphyrin IX pretreatment group). Arterial blood gases, bronchoalveolar lavage fluid (BALF), and serum pulmonary surfactant-associated protein A (SP-A) were measured in each group. The changes in the AEC-II ultrastructure were observed under an electron microscope. The HO-1 protein expression was detected by immunohistochemistry, and HO-1 messenger ribonucleic acid (mRNA) was detected by polymerase chain reaction. The results of this study showed that there were significant differences in PO 2 , pCO 2 , and PaO 2 /FiO 2 among the different groups (p < 0.05). The difference between BALF and SP-A in each group was statistically significant (p < 0.01). There were also significant differences in the integrated optical density of the HO-1 protein expression and HO-1 mRNA in the pulmonary tissue of the different groups (p < 0.05 or p < 0.01). The results of the electron microscopy showed that AEC-II were relatively irregular in the OA group. The cells degenerated and even disintegrated, the microvilli on the cell surface decreased, the lamellar bodies in the cytoplasm were evacuated, and some were discharged into the alveolar cavity. The above-mentioned changes in the OA + PR group were lower than in the OA group, while the changes were greater in the OA + IX group, compared with those in the OA group. We conclude that PR can significantly increase the expression of HO-1 in pulmonary tissues and reduce pulmonary injury, and, therefore, protect the AEC-II.

Alveolar epithelial type II (AT2) cells secrete pulmonary surfactant via lamellar bodies (LBs). Abnormalities in LBs are associated with pulmonary disorders, including fibrosis. However, high-content screening (HCS) for LB abnormalities is limited by the lack of understanding of AT2 cell functions. In the present study, we have developed LB cells harboring LB-like organelles that secrete surfactant proteins. These cells were more similar to AT2 cells than to parental A549 cells. LB cells recapitulated amiodarone (AMD)-induced LB enlargement, similar to AT2 cells of patients exposed to AMD. To reverse AMD-induced LB abnormalities, we performed HCS of approved drugs and identified 2-hydroxypropyl-β-cyclodextrin (HPβCD), a cyclic oligosaccharide, as a potential therapeutic agent. A transcriptome analysis revealed that HPβCD modulates lipid homeostasis. In addition, HPβCD inhibited AMD-induced LB abnormalities in human induced pluripotent stem cell-derived AT2 cells. Our results demonstrate that LB cells are useful for HCS and suggest that HPβCD is a candidate therapeutic agent for AMD-induced interstitial pneumonia.

Neonatal respiratory distress syndrome (NRDS) is a type of newborn disorder caused by the deficiency or late appearance of lung surfactant, a mixture of lipids and proteins. Studies have shown that lung surfactant replacement therapy could effectively reduce the morbidity and mortality of NRDS, and the therapeutic effect of animal-derived surfactant preparation, although with its limitations, performs much better than that of protein-free synthetic ones. Plasmalogens are a type of ether phospholipids present in multiple human tissues, including lung and lung surfactant. Plasmalogens are known to promote and stabilize non-lamellar hexagonal phase structure in addition to their significant antioxidant property. Nevertheless, they are nearly ignored and underappreciated in the lung surfactant-related research. This report will focus on plasmalogens, a minor yet potentially vital component of lung surfactant, and also discuss their biophysical properties and functions as anti-oxidation, structural modification, and surface tension reduction at the alveolar surface. At the end, we boldly propose a novel synthetic protein-free lung surfactant preparation with plasmalogen modification as an alternative strategy for surfactant replacement therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhuo, Rong, Wang, Parvin and Deng.)

Sphingomyelin (SM) is a constituent of cellular membranes, while ceramides (Cer) produced from SM on plasma membranes serve as a lipid mediator that regulates cell proliferation, differentiation, and apoptosis. In the skin, SM also is a precursor of Cer, an important constituent of epidermal permeability barrier. We investigated the role of epidermal SM synthase (SMS)2, an isoform of SMS, which modulates SM and Cer levels on plasma membranes. Although SMS2-knockout (SMS2-KO) mice were not neonatal lethal, an ichthyotic phenotype with epidermal hyperplasia and hyperkeratosis was evident at birth, which persisted until 2 weeks of age. These mice showed abnormal lamellar body morphology and secretion, and abnormal extracellular lamellar membranes in the stratum corneum. These abnormalities were no longer evident by 4 weeks of age in SMS2-KO mice. Our study suggests that (1) exposure to a dry terrestrial environment initiates compensatory responses, thereby normalizing epidermal ichthyotic abnormalities and (2) that a nonlethal gene abnormality can cause an ichthyotic skin phenotype., (© 2021 S. Karger AG, Basel.)