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Summary: Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as supported by the high occurrence of periodontitis. In this case–control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients [male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real‐time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non‐remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease. ‐Significant correlation between P. gingivalis rate in total bacteria genomes and disease activity in terms of DAS28 values and remission status. ‐Oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to a more active disease. ‐Beyond citrullination and antibody production, P. gingivalis could be implicated in triggering a pro‐inflammatory state in rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

An inverted pH gradient across the cell membranes is a typical feature of malignant cancer cells that are characterized by extracellular acidosis and cytosol alkalization. These dysregulations are able to create a unique milieu that favors tumor progression, metastasis and chemo/immune-resistance traits of solid tumors. A key event mediating tumor cell pH alterations is an aberrant activation of ion channels and proton pumps such as (H+)-vacuolar-ATPase (V-ATPase). TM9SF4 is a poorly characterized transmembrane protein that we have recently shown to be related to cannibal behavior of metastatic melanoma cells. Here, we demonstrate that TM9SF4 represents a novel V-ATPase-associated protein involved in V-ATPase activation. We have observed in HCT116 and SW480 colon cancer cell lines that TM9SF4 interacts with the ATP6V1H subunit of the V-ATPase V1 sector. Suppression of TM9SF4 with small interfering RNAs strongly reduces assembly of V-ATPase V0/V1 sectors, thus reversing tumor pH gradient with a decrease of cytosolic pH, alkalization of intracellular vesicles and a reduction of extracellular acidity. Such effects are associated with a significant inhibition of the invasive behavior of colon cancer cells and with an increased sensitivity to the cytotoxic effects of 5-fluorouracil. Our study shows for the first time the important role of TM9SF4 in the aberrant constitutive activation of the V-ATPase, and the development of a malignant phenotype, supporting the potential use of TM9SF4 as a target for future anticancer therapies. [ABSTRACT FROM AUTHOR]

This paper focuses on the dynamic characterization approach to evaluate the conservation state of carbonate building stones of monumental structures. In particular, we report the use of elastic waves at an ultrasonic frequency of 54 kHz to define quantitatively some dynamic properties of carbonate rock types used as building materials. Measurements of compressional and shear wave velocities have been carried out and the relationship between some physical properties of the investigated rocks and these geophysical measurements have been evaluated. The ultrasonic data were also supplemented by a petrographical study of these rocks to correlate their petrophysical features with the elastic ones. Based on the results of the laboratory measurements, in situ applications on a significant monumental structure have been also carried out to check zones of weakness and to assess the state of deterioration of the investigated stones. A comparison of laboratory and in situ results confirms that dynamic characterization is a useful approach. [ABSTRACT FROM AUTHOR]

Fais S [Istituo Superiore di Sanità (National Institute of Health), Rome, Italy]. Proton pump inhibitor-induced tumour cell death by inhibition of a detoxification mechanism (Symposium). J Intern Med 2010; 267:515–525. This review presents a possible new approach against cancer, as represented by inhibition of proton pumps, a mechanism used by tumour cells to avoid intracellular accumulation of toxic substances. Proton pump inhibitors (PPIs) belong to a family of pro-drugs that are currently used in the treatment of peptic diseases needing acidity to be activated. PPIs target the acidic tumour mass, where they are metabolized, thus blocking proton traffic. Proton pump inhibition triggers a rapid cell death as a result of intracellular acidification, caspase activation and early accumulation of reactive oxygen species into tumour cells. As a whole, the devastating effect of PPIs on tumour cells suggest the triggering of a fatal cell toxification. Many human tumours, including melanoma, osteosarcoma, lymphomas and various adenocarcinomas are responsive to PPIs. This appears highly conceivable, in as much as almost all human tumours are acidic and express high levels of proton pumps. Paradoxically, metastatic tumours appear to be more responsive to PPIs being more acidic than the majority of primary tumours. However, two clinical trials test the effectiveness of PPIs in chemosensitizing melanoma and osteosarcoma patients. Indeed, tumour acidity represents a very potent mechanism of chemoresistance. A majority of cytotoxic agents, being weak bases, are quickly protonated outside and do not enter the cells, thus preventing drugs to reach specific cellular targets. Clinical data will provide the proof of concept on the use of PPIs as a new class of antitumour agent with a very low level of systemic toxicity as compared with standard chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Tumour cells release vesicular structures, defined as microvesicles or exosomes, carrying a large array of proteins from their originating cell. The expression of antigenic molecules recognized by T cells has originally suggested a role for these organelles as a cell-free antigen source for anticancer vaccines. However, recent evidence shows that tumour exosomes may also exert a broad array of detrimental effects on the immune system, ranging from apoptosis in activated antitumour T cells to impairment of monocyte differentiation into dendritic cells and induction of myeloid suppressive cells. Immunosuppressive exosomes of tumour origin can be found in neoplastic lesions and sera from cancer patients, implying a potential role of this pathway in in vivo tumour progression. Through the expression of molecules involved in angiogenesis promotion, stromal remodelling, delivery of signalling pathways through growth factor/receptor transfer, chemoresistance and genetic intercellular exchange, tumour exosomes could represent a versatile tool for moulding host environment. Hence, their secretion by neoplastic cells may in the future become a novel pathway to target for therapeutic intervention in cancer patients.Cell Death and Differentiation (2008) 15, 80–88; doi:10.1038/sj.cdd.4402237; published online 12 October 2007 [ABSTRACT FROM AUTHOR]

Activating BRAF or NRAS mutations have been found in 80% of human sporadic melanomas, but only one of these genetic alterations could be detected in each tumour. This suggests that BRAF and NRAS ‘double mutants’ may not provide advantage for tumour growth, or may even be selected against during tumorigenesis. However, by applying mutant-allele-specific-amplification-PCR method to short-term melanoma lines, one out of 14 tumours was found to harbour both BRAFV600E and the activating NRASQ61R mutations. On the other hand, analysis of 21 melanoma clones isolated by growth in soft agar from this tumour indicated that 16/21 clones harboured a BRAFV600E, but were wild-type for NRAS, whereas the remaining had the opposite genotype (NRASQ61R/wild-type BRAF). When compared to BRAFV600E clones, NRASQ61R clones displayed reduced growth in soft agar, but higher proliferative ability in vitro in liquid medium and even in vivo after grafting into SCID/SCID mice. These data suggest that NRAS and BRAF activating mutations can coexist in the same melanoma, but are mutually exclusive at the single-cell level. Moreover, the presence of NRASQ61R or BRAFV600E is associated with distinct in vitro and in vivo growth properties of neoplastic cells.Oncogene (2006) 25, 3357–3364. doi:10.1038/sj.onc.1209379; published online 6 February 2006 [ABSTRACT FROM AUTHOR]

The acquisition of a cell polarity is a crucial requirement for a number of cellular functions, including apoptosis. Cell polarization is an actin cytoskeleton-driven process, through a connection between actin and an increasing number of membrane proteins. The major actors in this connection are ezrin, radixin and moesin, a family of proteins with a high level of homology. Their structure includes an epitope that links to membrane proteins and the other that binds to the actin molecule. In this review we discuss recent data showing that the Fas linkage to the actin cytoskeleton is ezrin mediated and it is an essential requirement for susceptibility to the Fas-mediated apoptosis. The ezrin region responsible of Fas binding consists of 18 aminoacids mapped on the median lobe of the ezrin FERM domain. This binding is specific and of key importance in the control of cell homeostasis. Moreover, Fas-ezrin co-localization, ezrin phosphorylation and early acquisition of susceptibility to Fas-mediated apoptosis, may have a role in some human diseases in which programmed cell death seems to be a central pathogenetic mechanism, such as AIDS. [ABSTRACT FROM AUTHOR]

CD95(APO-1/Fas)-mediated apoptosis of bystander uninfected T cells exerts a major role in the HIV-1-mediated CD4+ T-cell depletion. HIV-1 gp120 has a key role in the induction of sensitivity of human lymphocytes to CD95-mediated apoptosis through its interaction with the CD4 receptor. Recently, we have shown the importance of CD95/ezrin/actin association in CD95-mediated apoptosis. In this study, we explored the hypothesis that the gp120-mediated CD4 engagement could be involved in the induction of susceptibility of primary human T lymphocytes to CD95-mediated apoptosis through ezrin phosphorylation and ezrin-to-CD95 association. Here, we show that gp120/IL-2 combined stimuli, as well as the direct CD4 triggering, on human primary CD4+T lymphocytes induced an early and stable ezrin activation through phosphorylation, consistent with the induction of ezrin/CD95 association and susceptibility to CD95-mediated apoptosis. Our results provide a new mechanism through which HIV-1-gp120 may predispose resting CD4+T cell to bystander CD95-mediated apoptosis and support the key role of ezrin/CD95 linkage in regulating susceptibility to CD95-mediated apoptosis.Cell Death and Differentiation (2004) 11, 574-582. doi:10.1038/sj.cdd.4401374 Published online 23 January 2004 [ABSTRACT FROM AUTHOR]

We have recently shown that a human CD4+ T cell line (CEMSS) acquires the permissiveness to M-tropic strains and primary isolates of HIV-1 after transplantation into SClD mice. This permissiveness was associated with the acquisition of a memory (CD45RO+) phenotype as well as of a functional CCR5 coreceptor. In this study, we have used this model for investigating in viva the relationships between HIV-1 infection, apoptosis and T cell differentiation. When an in viva HIV-1 infection was performed, the CEM cell tumors grew to a lower extent than the uninfected controls. CEM cells explanted from uninfected SClD mice (ex viva CEM) underwent a significant level of spontaneous apoptosis and proved to be CD45RO+, Fas+ and Fas-L+, while Bcl-2 expression was significantly reduced as compared to the parental cells. Acute HIV-1 infection markedly increased apoptosis of uninfected ex viva CEM cells, through a Fas/Fas-L-mediated autocrine suicide/ fratricide, while parental cells did not undergo apoptosis following viral infection. The susceptibility to apoptosis of ex viva CEM cells infected with the NSI strain of HIV-1, was progressively lost during culture, in parallel with the loss of Fas-L and marked changes in the Bcl-2 cellular distribution. On the whole, these results are strongly reminiscent of a series of events possibly occurring during HIV-1 infection. After an initial depletion of bystander CD4+ memory T cells during acute infection, latently or chronically infected CD4+ T lymphocytes are progressively selected and are protected against spontaneous apoptosis through the development of an efficient survival program. Studies with human cells passaged into SClD mice may offer new opportunities for an in viva investigation of the mechanisms involved in HIV-1 infection and CD4+ T cell depletion. [ABSTRACT FROM AUTHOR]

Leukocyte adhesion to kidney cells is an early event in renal inflammation, such as glomerulonephritis. We developed an experimental model of monocyte adhesion to cultured human mesangial cells. U-937 myelomonocytic leukaemia cells, similar to peripheral blood human monocytes, irreversibly bound to mesangial cell monolayers upon 30–180 min coincubations (to a max. of 13600±1100/cm monolayer), as assessed by cell counting, U-937 labelling with H-thymidine, and colorimetry of nuclear staining with crystal violet. Adhesion was enhanced in mesangial cells proliferating in response to 17% fetal bovine serum, indicating expression of a proinflammatory phenotype. lipopolysaccharide (LPS), tumour necrosis factor-α (TNF-α) and protein kinase C activation with phorbol myristate acetate (PMA) potentiated monocyte binding during either coincubation or 24-h pretreatment (0.1 μM PMA, +200±21%). Binding was also promoted by pretreatment with vasoconstrictors, such as the thromboxane A mimetic, U-46619 (10 nM-1 μM, max. +35±3%), or 1 μM angiotensin II (+64±4%). To elucidate the mechanisms of monocyte adhesion, we analysed the adhesion molecules expressed by human mesangial cells, employing reverse transcription/polymerase chain reaction to detect ICAM-1, VCAM-1 and E-selectin gene expression. Proliferating cells express VCAM-1 and ICAM-1, confirmed by immunocytochemical staining and 79±3% inhibition of stimulated adhesion by pretreatment of mesangial cells with an anti-ICAM-1 monoclonal Ab. E-selectin transcription was not detectable. VCAM-1, but not ICAM-1, mRNA content was increased by LPS and TNF-α, while immunostaining of fixed cells indicated stimulation of ICAM-1 and VCAM-1 protein by LPS, TNF-α and, to a lesser extent, U-46619. Thus, post-transcriptional regulation of ICAM-1/VCAM-1 or expression of other adhesion molecules may account for vasoconstrictor-enhanced binding of monocytes to human mesangial cells. These findings underscore the importance of mesangial ‘priming’ by inflammatory or vasoactive mediators in leukocyte chemoattraction during glomerular disease. [ABSTRACT FROM PUBLISHER]

Immunological abnormalities present in HIV- 1-infected individuals often reflect an imbalance of cytokine production. The HIV-1 gp120 has the ability to induce a number of cytokines, and to enhance immunoglobulin release by normal peripheral blood mononuclear cells (PBMC) in vitro, in the absence of IL-2 production and of lymphoproliferation. This study provides evidence that gp120 is a potent IL-10 inducer in normal PBMC cultures. The pattern of other cytokines induced by gp120 includes interferon-alpha (IFN-α) and IFN-γ, tumour necrosis factor-alpha (TNF-α), IL-6, IL-1α and -β, and not IL-2 and IL-4. These findings further define the pattern of cytokine release induced by gp120 on human resting PBMC. Furthermore, the present findings roughly parallel those observed both in the sera of patients and in the mononuclear cells from HIV+ individuals early after infection, suggesting that gp120 could be a good candidate as one of the agents responsible for cytokine dysregulation observed in HIV-1-infected individuals. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that serum factors present in Crohn's disease interfere with the process of lymphocyte activation. The mitogen-induced proliferation and the expression of early activation antigens by normal lymphocytes cultured in the presence of either Crohn's disease sera or sera from different controls were evaluated. The mitogen-induced proliferation was significantly impaired in the presence of Crohn's disease sera. These sera markedly inhibited the mitogen-induced interleukin-2 receptor (IL-2R) expression (48% inhibition), while the effect of sera on the expression of the transferrin receptor and the 4F2 antigen was much less pronounced. Diafiltration experiments showed that the inhibitory effect was confined to a 30-50-kD serum fraction. Such a serum property was not related to the patients' disease activity and disappeared after surgical removal of the affected bowel. The capability of inhibiting the mitogen-induced IL-2R expression was not restricted to Crohn's disease and was observed with sera from other inflammatory and neoplastic gastrointestinal disorders. This study indicates that a marked inhibition of the IL-2R is a mechanism underlying the immunosuppressive property of the serum in Crohn's disease and in other gastrointestinal conditions. [ABSTRACT FROM AUTHOR]

Colonic epithelial cells (CEC) were isolated from actively inflamed mucosa of IBD patients and checked for HLA-DR. HLA-DP, and HLA-DQ. Half of the freshly isolated CEC from IBD tissue expressed DR, and one third were positive for DP and DQ. Normal human CEC were then cultured for 24 h and their expression of these markers in response to different types of in vitro stimulation was investigated. A significant increase in the expression of DR, DP and DQ was observed in response to the nonspecific mitogen phytohaemagglutinin (PHA), the lymphokine gamma-interferon (γ-IEN) and the epidermal growth factor (EGF). The enhancement of DR expression was more marked than that of DP and DQ. The effect ofγ-IFN was more rapid and significantly more marked than that of either PHA and EGF for all three antigens. EGF appeared to be more potent than PHA in enhancing the expression of DP and DQ. The data from this study indicate that HLA-D region antigens can be induced on human CEC by different types of stimuli and provide further evidence that the expression of these markers in the colonic epithelium is a normal event the magnitude of which can increase under various circumstances. The data also suggest that the increased expression of HLA-D region antigens by IBD CEC occurs as a result of different mechanisms, and that this expression is an indicator of the active participation of the colonic epithelium to the mucosal inflammatory response. [ABSTRACT FROM AUTHOR]

The colonic epithelial expression of HLA-DR molecules and of other markers of cell membrane perturbation was investigated by immunofluorescence in biopsy specimens from patients with ulcerative colitis and Crohn's disease. It was found that in virtually all specimens from either groups showing active inflammation there was a diffuse epithelial expression of HLA-DR molecules. There was no relation between the grading of active inflammation and the epithelial expression of HLA-DR antigens. The epithelium of virtually al! specimens from the macro and microscopically uninvolved areas of patients with active colitis and from patients with histologically quiescent colitis showed no detectable expression of HLA-DR+ molecules. The counts of isolated lamina propria lymphocytes expressing the transferrin receptor and the interleukin 2 receptor were higher in specimens with HLA-DR- epithelium than In those with a HLA-DR epithelium. Twenty-nine of the 35 (83%) HLA-DR positive specimens proved to express the 4F2 antigen on their epithelium and 19 (54%) were positive for the transferrin receptor. All sections positive for either the 4F2 antigen or the transferrin receptor were also HLA-DR positive while all HLA-DR negative sections were also negative for either of the two other markers. Data in this study suggest that in active IBD the epithelial participation in active inflammation is associated with a sequence of cell membrane rearrangements, and that the expression of HLA-DR molecules is a part of this sequence. [ABSTRACT FROM AUTHOR]

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Identification of cell-derived molecules on infectious human immunodeficiency virus type 1 (HIV-1) particles may be helpful in investigating mechanisms of HIV infection and in vaccine studies. Some of these molecules were detected on HIV-1 virions in previous studies, but rather elaborate methods were used. The method presented here allows an extensive characterization of the cell surface molecules associated with HIV-1 by capturing virus particles on monoclonal antibodies to cell membrane antigens bound to plastic wells. Binding of infectious virus was assessed by adding permissive target cells (C8I66) and determining viral replication. With this procedure, β2-microglobulin, HLA-DR, intercellular adhesion molecule-1, and leukocyte function antigen-I were found on HIV-1 particles from laboratory strains and primary clinical isolates. In contrast, CDI9, CD4, and CD8 molecules were not detected. [ABSTRACT FROM PUBLISHER]

Multinucleated giant cells are an important feature of the granulomatous reaction in Crohn's disease (CD) but their cellular origin is poorly understood. The aim of this study was to discover if intestinal macrophages are capable of generating multinucleated giant cells in vitro in response to cytokine stimulation. Human intestinal macrophages were isolated from the intestinal mucosa of CD and uninflamed surgical specimens. Isolated macrophages were cultured in chamber slides with and without exposure to a panel of cytokines and cell activators. Cell fusion, multinucleated giant cells formation, and the expression of adhesion molecules were assessed at various time intervals. In contrast with the autologous peripheral monocytes cell fusion was very poor in cultures of control intestinal macrophages and virtually no multinucleated giant cells were seen. Control intestinal macrophages seemed to poorly express the adhesion molecules required for cell to cell adhesion and fusion, namely ICAM-1 and LFA-1. None of these functions was affected by the exposure to cytokines, including interferon gamma. In cultures of macrophages isolated from CD tissues multinucleated giant cell formation spontaneously occurred as early as three days and was not enhanced by the addition of cytokines. CD macrophages seemed to highly express both ICAM-1 and LFA-1. These data show that human intestinal macrophages are unable to form multinucleated giant cells in response to stimuli and support the concept that they are downregulated in a number of functions. The data also suggest that macrophages participating in the ganulomatous reaction in CD are recruited from the circulation. [ABSTRACT FROM PUBLISHER]

The virus induced production of interferon alpha by human intestinal lamina propria mononuclear cells was investigated. Intestinal and autologous peripheral cells from control subjects and patients with Crohn's disease were cultured in vitro with and without stimulation with the Newcastle disease virus. Interferon alpha was measured and characterised in the culture supernatants after 12 hours and the kinetics of production was evaluated over the following four days of culture. No detectable interferon alpha was found in cultures of unstimulated intestinal and autologous peripheral mononuclear cells from controls and Crohn's disease whereas interferon alpha was released in all cultures stimulated with the virus. In all 12 hours experiments in both groups, virus stimulated intestinal mononuclear cells yielded significantly less interferon alpha than the autologous peripheral cells. The kinetics experiments showed that control intestinal mononuclear cells appeared to be poorly responsive to virus stimulation showing a release of interferon alpha significantly lower than that of the autologous peripheral cells. The interferon alpha release at day 4 by control cells (either intestinal or peripheral) did not differ from that measured after the first 12 hours. In contrast, the interferon alpha produced by Crohn's disease cells progressively increased during the culture period and the amount of interferon alpha measured at day 4 was significantly higher than that released at 12 hours. These data suggest that normal human intestinal mononuclear cells are down regulated in their capability of producing interferon alpha and that in Crohn's disease their activation for this function is enhanced. These data also suggest that in Crohn's disease intestinal mononuclear cells exhibit a transient hyporesponsiveness to in vitro stimulation possibly related to massive in vivo exposure to interferon alpha inducers. [ABSTRACT FROM PUBLISHER]

Jejunal biopsies from 16 treated coeliac disease patients and from nine controls were cultured with and without a peptic-tryptic digest of gliadin. Cultures with a peptic-tryptic digest of maize prolamins were also undertaken. Frozen sections of baseline and cultured mucosa were stained by immunofluorescence with an anti-HLA-DR monoclonal antibody. Before culture the villous epithelium from both controls and treated coeliac disease expressed DR molecules while the crypt epithelium did not. When biopsies from treated coeliac disease were cultured with gliadin the expression of DR was enhanced in the crypt epithelium in eight of 14 cultures and in 11 of 14 was reduced or absent on the villous epithelium. No change was observed in control cultures. We conclude that gliadin is capable of inducing HLA-DR on the crypt epithelium of in vitro cultured coeliac disease mucosa, providing indirect evidence that gliadin may activate cell mediated immune mechanisms within the small bowel mucosa. This model could prove useful in identifying the immunogenic sequence(s) of gliadins and related prolamins. [ABSTRACT FROM PUBLISHER]

The spontaneous induced release of interferon gamma (IFN gamma) by cultured intestinal lamina propria lymphocytes was investigated in patients with Crohn's disease. In contrast to normal lymphocytes, intestinal lymphocytes from these patients spontaneously released IFN gamma and seemed to contain IFN gamma in their cytoplasm. Autologous peripheral lymphocytes did not release IFN gamma. When stimulated with interferon inducers lamina propria lymphocytes from Crohn's disease tissue showed an increase in IFN gamma release 24 hours after induction with no appreciable further increase over the next two days of culture, while in control cells, either peripheral or intestinal, IFN gamma release progressively increased, peaking 72 hours after induction. These findings indicate that in Crohn's disease the intestinal lymphocytes are stimulated in vivo to produce IFN gamma and that the spontaneous IFN gamma production is compartmentalised to the gut lymphocytes. These data support the concept that locally released IFN gamma has a crucial role in cell interactions in the lamina propria and contribute to the locally occurring immune phenomena in Crohn's disease, including the increased epithelial expression of major histocompatibility complex class II antigens. [ABSTRACT FROM PUBLISHER]

In the present study the state of activation of either peripheral blood and intestinal lamina propria mononuclear cells in Crohn's disease was defined by investigating the expression of early activation antigens (namely the 4F2 antigen, the transferrin receptor and the interleukin-2 receptor). The expression of 4F2 and T9 antigens was greatly increased--in the peripheral blood and in the intestinal lamina propria whereas the proportion of interleukin-2 receptor bearing cells was much less pronounced. The counts of early activation antigens bearing cells in the lamina propria were quite comparable with those of the autologous peripheral cells. In the peripheral blood counts of 4F2 and T9 positive cells were very high in patients with active Crohn's disease but patients with quiescent disease also had a significantly raised proportion of 4F2 and T9 bearing cells. Only in those patients with no evidence of macroscopic disease (namely those resected without recurrence) the counts of early activation antigens bearing cells were within the normal range. The in vitro mitogen induced expression of early activation antigens on either peripheral and intestinal mononuclear cells of patients with Crohn's disease proved to be both quantitatively and qualitatively similar to that of the controls showing the full expression of 4F2, transferrin receptor, and interleukin-2 receptor. While demonstrating that in Crohn's disease there was no intrinsic defect of generation and expression of growth factors receptors by peripheral and intestinal lymphocytes, these results showed that there was a divergence in the expression of early activation antigens in vivo and in vitro. This would indicate that in Crohn's disease there is an in vivo increased population of preactivated rather than fully activated lymphocytes consisting of 4F2 and T9 bearing cells. The high proportion of these cells in the peripheral blood and in the intestine suggests that a chronic immune activation is present in these patients outside as well as within the affected bowel. [ABSTRACT FROM PUBLISHER]

HIV-1 acquires cell membrane proteins during budding. The cell membrane proteins (CMP) profile of laboratory HIV-1 strains grown in different host cells was established, by using an immobilized antibody capture (IAC), to verify whether CMPs present on HIV-1 correlate with its host cell origin. HIV-1 grown in different cell lines incorporates cell markers such as CD3, CD19, CD14, CD31 and IL 2-R, according to the distinctive expression of these antigens on the host cells. Furthermore, also T-tropic and monocytotropic HIV-1 strains display host cell specific markers, supporting the hypothesis that virus associated CMPs are a marker of host cell origin. [ABSTRACT FROM AUTHOR]

Human umbilical vein endothelial cells (HUVEC) can be abortively infected with HIV-1, but virus production is rescued by the addition of T cells. Monoclonal antibody (Mab) to ICAM-1, but not its Fab' fragment or MAbs to LFA-1 and PECAM-1, increases HIV-1 infection of HUVEC by enhancing HIV-1 absorption. Enhancement by anti ICAM-1 is probably due to a bridging effect different from the ADE mediated by anti-gp120 that involves FcR or CR-mediated capture of the virus-antibody complex. Since antibodies to cell membrane molecules are present in HIV-1 infected patients, the ADE mediated by such a mechanism can be important in AIDS pathogenesis. [ABSTRACT FROM AUTHOR]

Whether inflammatory bowel diseases (IBD) can be classified as autoimmune disorders is not established. Since circulating acid-labile interferon-alpha (IFN-α) is believed to reflect autoimmune reactions, we tested sera from two groups of IBD patients for the presence of circulating IFN, No detectable IFN was found in 51 serum samples of IBD patients. Furthermore, in no serum sample of IBD patients were neutralizing anti-IFN antibodies found. In contrast, acid-labile IFN-α was present in sera from 21/52 HIV-infected and from 6/14 systemic lupus erythematosus patients. These observations provide evidence that IBD differs from systemic autoimmune disorders, at least for the presence of circulating IFN. [ABSTRACT FROM AUTHOR]

The association between the expression of HLA-DR antigens on cervical epithelium and the local immune state of activation in colposcopically obtained biopsy specimens from patients with histologically documented wart virus infection was investigated. In normal cervical epithelium no HLA-DR staining was detected. No or few IL-2R positive cells were found in the contiguous sections. HLA-DR was expressed by epithelial cells in six out of the 14 samples of wart virus infection. The pattern of fluorescence was focal, but strong and diffuse, to the whole epithelial layer. In the six samples with HLA-DR positive epithelium the numbers of IL-2R positive cells in the lamina propria were strongly increased, ranging between 75 and 90%. HLA-DR expression by cervical epithelium was observed in only two of 12 samples from patients with mixed epithelial non-virus related abnormalities. No increase in the numbers of IL-2R positive cells was observed in this group of patients. Additionally, no significant differences in terms of T lymphocyte infiltrate were found among the three groups. The results indicate that wart virus infection is associated with enhanced HLA-DR epithelial expression and they lend support to the concept that in the human cervix the epithelium actively participates in the local immune response. [ABSTRACT FROM PUBLISHER]