EXPRESSION AND SHEDDING OF INTERCELLULAR-ADHESION MOLECULE-1 AND LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-3 BY NORMAL AND SCLERODERMA FIBROBLASTS - EFFECTS OF INTERFERON-GAMMA, TUMOR NECROSIS FACTOR-ALPHA, AND ESTROGEN

Objective. To examine intercellular adhesion molecule 1 (ICAM-1) and l ymphocyte function-associated antigen 3 (LFA-3) in cultures of normal and systemic sclerosis (SSc) dermal fibroblasts. Methods. The surface and soluble forms of ICAM-1 and LFA-3 were measured by flow cytometry and capture enzyme-linked immunosorbent assay, respectively. Results. Surface ICAM-1 was significantly higher on SSc fibroblasts compared wi th normal controls. beta-estradiol did not directly enhance ICAM-1 or LFA-3 expression in either normal or SSc cells, but significantly augm ented the cytokine-induced increase in ICAM-1. Soluble ICAM-1 (sICAM-1 ) and sLFA-3 were detected in fibroblast cultures. While no difference was found in the level of sLFA-3, the shedding of sICAM-1 was signifi cantly increased (P < 0.001) in cells from SSc patients. Conclusion. S Sc fibroblasts express intrinsically elevated levels of surface ICAM-1 and release higher levels of sICAM-1 in vitro. Increased expression o f ICAM-1 by interferon-gamma and tumor necrosis factor alpha alone, an d the further induction in combination with beta-estradiol may underli e an aspect of fibroblast dysfunction in SSc and the female predisposi tion to the disease.