Objective: To investigate the possible role of integrins and cell adhesion molecules in the pathogenesis of the mononuclear cell infiltration and fibrosis of skin that occurs in systemic sclerosis (SSc).
Methods: The presence and topographic distribution of beta 1, beta 2, and beta 4 integrins, as well as of endothelial leukocyte adhesion molecule 1 (ELAM-1) and intercellular adhesion molecule 1 (ICAM-1), was examined immunohistochemically in affected skin from 8 patients with rapidly progressive SSc of recent onset. The expression of the beta 1 integrin gene was also investigated by in situ hybridization with a human sequence-specific complementary DNA.
Results: The presence of beta 1 integrin epitopes and the corresponding messenger RNA within inflammatory cells surrounding small vessels was demonstrated in SSc skin but not in normal skin. Lymphocytes positive for beta 2 integrin were also found only in SSc skin, and they appeared in close proximity to small blood vessels and collagen bundles. Immunostaining for beta 4 integrin epitopes revealed no differences between normal and SSc skin. ELAM-1 and ICAM-1 monoclonal antibodies, which identify epitopes indicative of endothelial cell activation, stained endothelial cells in SSc skin but not normal skin.
Conclusion: These observations suggest that the complex interactions of beta 1 and beta 2 integrins, as well as ELAM-1 and ICAM-1, may be intimately involved in the pathogenesis of SSc, perhaps by mediating the homing and targeting of pathogenetic lymphocytes to the affected tissues.