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Biomedical subjects

I Kellner

Publications and source records attributed to I Kellner.

8 recordsLinked to original sources

Differential expression of adhesion molecules on infiltrating cells in inflammatory dermatoses.

BACKGROUND: Adhesion molecules and their ligands are involved in coordination of the activities of the immune system. OBJECTIVE: To evaluate whether adhesion molecules are relevant in the pathogenesis of inflammatory dermatoses, we analyzed the expression pattern of many of these molecules. METHODS: The expression of 10 members of the integrin and immunoglobulin superfamilies was mapped by means of immunohistochemical techniques in biopsy specimens of psoriasis (n = 15), pityriasis lichenoides (n = 11), parapsoriasis en plaques (n = 11), contact dermatitis (n = 7), and lichen planus (n = 5). RESULTS: In all investigated skin diseases, almost every infiltrating cell expressed lymphocyte function-associated antigens 1 and 3 as well as very late activation (VLA) antigens 4 and 5. The subepidermal infiltrate differed with regard to the expression of VLA-1, VLA-3, and VLA-6, which was high in lichen planus and moderate or absent in the other dermatoses. The intraepidermal lymphocytes in psoriasis and pityriasis lichenoides were VLA-1 positive, whereas the subepidermal infiltrate lacked this marker. CONCLUSION: The differential upregulation of adhesion molecules in the mononuclear infiltrate and on keratinocytes demonstrates their importance in the pathogenesis of cutaneous inflammation.

Antigens, Differentiation↗

Expression of adhesion proteins involved in cell-cell and cell-matrix interactions in the skin of patients with progressive systemic sclerosis.

BACKGROUND: Lymphocytic infiltration and activation of connective tissue metabolism in the early phase of progressive systemic sclerosis (PSS, scleroderma) may be critically influenced by cellular adhesion molecules (CAMs), which mediate cell-cell and cell-extracellular matrix interactions. OBJECTIVE: The tissue distribution might demonstrate a pathogenetic role of these adhesion molecules in early edematous and chronic fibrotic scleroderma. METHODS: We investigated by immunohistochemical techniques the in situ expression and distribution of beta 1 and beta 2 integrins, selectins, and CAMs of the immunoglobulin superfamily in patients with scleroderma. RESULTS: In the early disease stage a moderate percentage of perivascular CD3+/CD4+/TCR alpha/beta + lymphocytes showed expression of the alpha 3, alpha 5, and beta 1 chains and, to a lesser degree, of the alpha 1, alpha 2, alpha 4 and alpha 6 subunits. In contrast to chronic PSS, LFA-1 alpha, LFA-1 beta and ICAM-1 expression on mononuclear infiltrating cells was seen more frequently in acute scleroderma. Different percentages of fibroblasts expressed alpha 1-, alpha 3-, alpha 5- and beta 1-integrin chains. In acute PSS ICAM-1 was expressed especially by fibroblasts located around perivascular inflammatory infiltrates as well as by endothelial cells (ECs). A few ECs expressed alpha 2 beta 1 integrins. CONCLUSION: Our observations suggest that CAMs are intimately involved in early pathogenetic events in scleroderma, mediating cellular interactions between lymphocytes, ECs, and fibroblasts, as well as homing and tissue targeting of mononuclear infiltrating cells.

Acute Disease↗

Role of beta 1-integrins in epidermotropism of malignant T cells.

To better understand the molecular mechanisms of epidermotropism, we immunohistochemically analyzed the expression pattern of adhesion molecules belonging to the integrin and immunoglobulin superfamilies in cases of mycosis fungoides (MF) (n = 15), pleomorphic T cell lymphoma (n = 10), and high-grade T cell lymphoma (n = 7). The cutaneous T cell lymphomas (CTCLs) investigated were categorized into cases with or without epidermotropism. Focal neoexpression of ICAM-1 on keratinocytes was restricted to epidermotropic lymphomas. Both LFA-1 and LFA-3 were expressed on infiltrating cells in all cases investigated. In contrast, beta 1-integrins showed differential expression, most prominent in the case of VLA-1 and VLA-6: These molecules were present on infiltrating cells in most cases with epidermotropic MF and absent in most other CTCLs. We conclude that the phenomenon of epidermotropism might involve different sets of adhesion molecules in different entities of CTCL, with VLA-1 being the most influential beta 1-integrin in the case of MF.

Antibodies, Monoclonal↗

Overexpression of extracellular matrix receptors (VLA-3, 5 and 6) on psoriatic keratinocytes.

The potential role of adhesion molecules in the pathophysiology of psoriasis was investigated and the pattern of expression of the cell-surface receptors ICAM-1, LFA-3, and VLA-1, 2, 3, 4, 5 and 6 was determined in biopsies of skin from patients with psoriasis (n = 12) and from normal skin (n = 12). There were no differences in the intensity or localization of the adhesion molecules VLA-1, 2 and 4 and LFA-3. In contrast, VLA-3 and VLA-6, which are restricted to the basal keratinocytes in normal skin, were overexpressed in the spinous cells in psoriatic skin. ICAM-1 and VLA-5, which are not expressed by keratinocytes in normal skin, were focally induced, especially in cells above elongated rete ridges and where there was an infiltrate with intraepidermal granulocytes and lymphocytes.

Antibodies, Monoclonal↗

Induction and upregulation of adhesion receptors in oral and dermal lichen planus.

The expression pattern of well-defined cell surface adhesion receptors called VLA-family, LFA-1 and ICAM-1 was determined semiquantitatively in biopsies of oral (n = 12) and dermal lichen planus (n = 5) and compared to normal uninvolved human oral mucosa (n = 12) and skin (n = 12) using an indirect immunoperoxidase technique. In both oral and dermal lichen planus, an induction of the beta 1-integrins VLA-1 and VLA-3 and an upregulation of VLA-6 was found in T cells infiltrating the basement membrane zone. These cell surface molecules function as receptors for collagen, fibronectin and laminin. A focal induction of ICAM-1 on basal keratinocytes could be detected at sites of intramucosal T cells. These results suggest that investigated adhesion receptors are crucially involved in the aggregation of T cells in both conditions. Further investigations have to be done to determine the functional role of these adhesion receptors in lichen planus.

Antigens, CD↗

Adhesion molecule mapping in normal human skin.

Adhesion molecules are a rapidly growing group of cell surface receptors providing cell-cell and cell-matrix interactions. Their physiological role in tissue homeostasis as well as cellular migration and differentiation is increasingly appreciated. In the present study we have analyzed the expression pattern of most adhesion molecules of the integrin family as well as of adhesion molecules belonging to the immunoglobulin superfamily in normal human skin. We provide evidence that expression of adhesion molecules in the various cutaneous cell systems follows a constant distribution. Moreover, the physiological mononuclear infiltrate of the skin also expresses a variety of adhesion molecules enabeling these cells to migrate or to reside within the skin. Furthermore, our results indicate that intercellular adhesion molecule-1 is not a prerequisite for lymphocyte epidermotropism as frequently stated. Our data provide a rational basis to analyze changing adhesion molecule expression in inflammatory and neoplastic skin diseases.

Adult↗

[Increased expression of adhesion molecules in oral lichen planus].

Adhesion of cells to other cells and to the matrix is the prerequisite for a multitude of cell interactions such as the emigration of circulating leukocytes to sites of inflammation, antigen-presentation, cell-mediated cytotoxicity, cell anchorage and differentiation. In the past few years, a large family of adhesion molecules has been defined which are receptors for these adhesion events. Using immunohistochemical techniques we analyzed the distribution pattern of adhesion molecules in the buccal mucosa of 12 patients with oral lichen planus reticularis and compared it with 12 specimens of normal oral mucosa. In lichen planus, a neo-expression of the antigens VLA-1, 3, 5 and 6, which are receptors for collagen, fibronectin and laminin, could be detected on T cells and macrophages infiltrating the basement membrane zone. ICAM-1, the specific ligand of LFA-1, normally only expressed by endothelial cells, showed a focal expression on basal keratinocytes at sites of intramucosal T cells. The abundance of adhesion molecules on leukocytes and keratinocytes in oral lichen planus is indicative of a special state of activation. It enables the leukocytes to penetrate the tissue, especially the basement membrane zone, to persist in this environment and to exercise their effector functions.

Antigens, CD↗