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.