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 βl and β2 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 +/ TCRα/,β + lymphocytes showed expression of the α3, α5, and β1 chains and, to a lesser degree, of the αl, α2, α4 and α6 subunits. In contrast to chronic PSS, LFA-lα, LFA-1β and ICAM-1 expression on mononuclear infiltrating cells was seen more frequently in acute scleroderma. Different percentages of fibroblasts expressed αl-, α3-, α5- and β1-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 α2β1 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 horning and tissue targeting of mononuclear infiltrating cells.