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.

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.

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.

[Increased expression of adhesion molecules in oral lichen planus]. / Gesteigerte Expression von Adhäsionsmolekülen bei oralem 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.

[Dento-alveolar surgery of the irradiated jaw: is infected osteoradionecrosis a preventable complication?]. / Dentoalveoläre Chirurgie im bestrahlten Kiefer: ist die infizierte Radioosteonekrose eine vermeidbare Komplikation?

In spite of preventive procedures before, during and after radiotherapy, profound caries and periodontal breakdown of healthy teeth occur. In the course of dentoalveolar surgery in the region of irradiated bone, the risk of development of an infected osteoradionecrosis can be reduced by prophylactic antibodies, prevention of extensive detaching of the periosteum careful osteotomy or extraction, complete smoothing of sharp alveolar ridges and epiperiosteal plastic coverage. When extensive dentoalveolar surgery is necessary, the application of prophylactic pre- and postoperative hyperbaric oxygen may reduce the rate of complications even more.

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.

Atopic dermatitis: influence of bacterial infections on human monocyte and neutrophil granulocyte functional activities.

In 15 patients with atopic dermatitis (AD) and without concomitant viral or bacterial infections, chemotaxis, superoxide-anion (O2-) generation, and beta-glucuronidase release of purified monocytes (MO) and neutrophils (PMN) were determined. Defined receptor-dependent stimulators (i.e., N-formyl-methionyl-leucyl-phenylalanine, C5a, and leukotriene B4, as well as native and opsonized zymosan particles) were used for phagocyte stimulation. PMN functional activities in response to the stimuli tested were found to be normal in patients with AD and without infections. MO from these patients revealed a slight enhancement of O2- production after stimulation with opsonized zymosan and a small increase of N-formyl-methionyl-leucyl-phenylalanine-induced chemotaxis. Other MO functions tested were within the normal range. However, investigations of MO and PMN functions during the course of concomitant bacterial infections of three patients with AD demonstrated striking alterations of cellular responsiveness. These changes ranged from enhanced to decreased phagocyte functions, depending on the activity of the infectious disorder. Chemotaxis of PMN and MO was depressed around the third day after onset of the infectious disease. In the beginning of infection, there was a decreased O2- generation and beta-glucuronidase release in PMNs. In MOs, both parameters were enhanced. The results of these investigations provide evidence that functional abnormalities of phagocytes observed in patients with AD are sequelae of concomitant skin infections and not signs of an intrinsic defect present in MOs and PMNs.

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.