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The density distribution pattern of eosinophils over discontinuous isotonic Percoll gradients from the blood of normal, asymptomatic allergic and non-allergic asthmatic individuals was investigated. There was a completely identical distribution pattern between the investigated groups. Analysis of the expression of surface markers for complement receptors CR1 and CR3 and immunoglobulin G receptor on eosinophils derived from the density bands 1·080, 1·085 and 1·090 g/ml supported this finding since they did not reveal differences in expression between the bands within one group but also not between the three groups. Eosinophils of the various density bands were further purified and stimulated in vitro to produce leukotriene C4 (LTC4) by the calcium ionophore A23187 or serum treated zymosan. Equal amounts of LTC4 were synthesized by the eosinophils of the various density bands within one group. However, it appeared that the eosinophils of all density bands of allergic and non-allergic asthmatics synthesized significantly more LTC4 than the eosinophils from normal individuals (five- to tenfold). Probably this indicates in viro priming of the eosinophils in asthmatic individuals which is not reflected by a change in density. Control experiments, dealing with possible artifacts due to the isolation procedure or the patient selection, to find differences in distribution patterns over discontinuous Percoll density gradients of the eosinophils of asthmatic compared to normal individuals failed to show such a difference. Therefore, the density distribution pattern of eosinophils over then gradients does not reflect cell activation, whereas LTC4 formation clearly does. This could mean that LTC4 formation is a more sensitive parameter for cell activation than density distribution or cell surface marker expression. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is considered a T-cell mediated disease. Activated T-cells. mainly of the CD4-subtype. arc abundantly present in lesional AD skin. Although not many in tact eosinophils are present, deposits of eosinophil derived major-basic-protein (MB?) and eosinophil-cationic-protein (FCP) suggest eosinophil involvement. Alter patch testing AD patients with aeroallergens, an eczematous reaction develops after 24 48 hr at the site of application. This patch test reaction shows macroscopic resemblance to lesional AD skin and does not take place in normal individuals, asthma and allergic rhinitis patients. Lymphocytes together with eosinophils infiltrate into the dermis 2-6 hr after allergen application. Twenty-four to forty-eight hours after patch testing, cosinophils are in an activated state since they release ECP (being EG2-positive). At this point in time eosinophils have also infiltrated the epidermis. Here they are E62- negative. Forty-eight to seventy-two hours after patch testing the eczematous reaction decreases. This coincides with disappearance of eosinophils from both the dermis and the epidermis: then. a dendritic staining pattern can he observed in the epidermis with anti-eosinophil peroxidase. Thus. eosinophils infiltrate the dermis and epidermis after patch testing AD patients with aeroallergens and release part of their granular constituents. Recent. in vitro investigations revealed that eosinophils from the circulation of Al) patients react more powerfully in in vitro test systems such as chemiluminescence, chemotaxis and endothelial adherence and transmigration. It is very likely that this activated (= primed) state is caused by the influence of lymphocyte-derived cytokines like IL-3. IL-5 and GM-CSF, since activated lymphocytes in the circulation (and tissue) may release these cytokines. The primed state of the eosinophils may facilitate tissue infiltration. The subsequent activation of eosinophils within the tissue leading to mediator release and the function of these mediators need to be further elucidated. The close similarity between the cellular events after a patch test reaction to aeroallergens in AD patients and those present in lesional AD skin suggests that the patch test reaction may be a helpful in vivo model to study the pathogenesis of AD. The prominent involvement of lymphocytes and eosinophils in this reaction also suggests sonic similarity with late phase reactions (LPR) observed in the skin alter intracutaneous allergen challenge. [ABSTRACT FROM AUTHOR]

The pathophysiology of photoageing of the skin has been studied extensively. Matrix metalloproteinases (MMPs) originating from keratinocytes and fibroblasts are thought to play a primary role in this process. Although neutrophils are potent producers of a wide array of proteolytic substances and are present in sunburned skin, their contribution to the pathophysiology of photoageing has been described only in murine studies.To determine the role of neutrophils in photoageing of human skin.Healthy white-skinned volunteers were recruited and their sun-protected buttock skin was exposed to solar-simulated radiation (SSR) in dose–response and time-course studies. Punch biopsies were taken and the influx of neutrophils and the expression of neutrophil elastase and MMPs was studied using immunohistochemical techniques andin situzymography.Neutrophil elastase and MMPs were detected only in skin irradiated with erythemogenic doses (≥ 1 minimal erythema doses) of SSR. Immunohistochemical double staining demonstrated neutrophils to be the major source of MMP-1, MMP-8 and MMP-9.In situzymography showed elastase, collagenase and gelatinase enzyme activity in those cells.Our study suggests that neutrophils participate in the process of photoageing of human skin as they infiltrate the skin and release enzymatically active elastase (neutrophil elastase), collagenase (MMP-1) and gelatinase (MMP-9). [ABSTRACT FROM AUTHOR]

Chronic proliferative dermatitis (cpd) is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm). The dermatitis is characterized by redness, hairloss, scaling, pruritus and histologically by epithelial hyperproliferation, infiltration of eosinophils, macrophages and mast cells. Lesions similar to those in the skin occur in the esophagus and forestomach. In this paper, we describe the effect of drug treatments directed against epidermal hyperproliferation (calcipotriene and etretinate), against inflammation (corticosteroids and dapsone) and against pruritus (loratidine and capsaicin). The criteria used to objectively estimate the effect of the treatment were 1) macroscopic evaluation of the lesions (cpd score), 2) degree of epithelial hyperproliferation assessed by BrdU incorporation and epithelial thickness, and 3) microscopic evaluation of the inflammatory cells in the skin samples. Treatment of the cpdm/cpdm mice with calcipotriene (5 μg/day for 3 weeks) inhibited epidermal proliferation and the number of eosinophils. Systemic etretinate treatment (30 μg/g/day for 3 weeks) was not very effective. Topical corticosteroids (0.05 μg/day, for 3 weeks) exerted a therapeutic effect on the hyperproliferation and the number of eosinophils. Oral dapsone treatment (34 μg/g/day, for 5 weeks) reduced the BrdU incorporation in the skin and the epithelial thickness in the esophagus. The anti-histamine loratidine (orally, 1.7 μg/g/day, for 4 weeks) reduced the severity of the lesions macroscopically, probably by suppressing the pruritus. Capsaicin (topically, 30 mM, for 5 weeks) also reduced the severity of the macroscopic observable lesions. Moreover, capsaicin reduced the dorsal and ventral epidermal thickness. The results from this and previous studies indicate that steroids (topically and systemically) and less strongly calcipotriene are the most effective treatments for the lesions observed in the cpdm/cpdm mice, since both hyperproliferation and... [ABSTRACT FROM AUTHOR]

Sputum from symptomatics asthmatics is a rich source of eosinophils from the respiratory tract. Following liquefaction of sputum with dithioerythritol (DTE), a cell suspension suitable for indirect double immunofluorescence with flow cytometry was obtained. Eosinophils were identified using anti-CD9 fluorescein conjugate, and particular surface markers measured with the relevant mouse MoAb followed by goat anti-mouse immunoglobulin phycoerythrin conjugate. Blood and sputum eosinophil surfacemarkers were determined in parallel from asthmatics not receiving steroid therapy. Sputum eosinophils were found to have considerably elevated levels of CD11b, a reflection of eosinophil activation. Sputum but not blood eosinophils were found to express ICAM-I (nine out of 11 cases) and HLA-DR (eight out of 11 cases). Furthermore, following culture of normal blood eosinophils with pooled T cell supernatants. ICAM-I and HLA-DR could be induced in vitro. The induction of eosinophil adhesion molecules such as ICAM-l and HLA-DR may influence eosinophil localization and function in asthma. [ABSTRACT FROM AUTHOR]

Langerhans cells (LC) are very potent antigen-presenting cells. In atopic disorders such as allergic rhinitis and atopic dermatitis LC are known to bear IgE surface molecules. IgE-positive LC can bind allergen and present it to T lymphocytes to induce an allergen-specific T-cell response and IgE synthesis. Therefore, IgE-bearing LC might play an important role in the triggering of the immune system to maintain ongoing IgE synthesis. The importance of the IgE-bearing LC in atopy has not been assessed but deserves further investigation to find out more about the part played by these cells, not only in the atopic disorders described here but also in others such as gastrointestinal allergy and allergic asthma. [ABSTRACT FROM AUTHOR]