Expression and shedding of intercellular adhesion molecule 1 and lymphocyte function–associated antigen 3 by normal and scleroderma fibroblasts.

Abstract

Objective. To examine intercellular adhesion molecule 1 (ICAM‐1) and lymphocyte 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 with normal controls. β‐estradiol did not directly enhance ICAM‐1 or LFA‐3 expression in either normal or SSc cells, but significantly augmented 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 significantly increased (P < 0.001) in cells from SSc patients. Conclusion. SSc fibroblasts express intrinsically elevated levels of surface ICAM‐1 and release higher levels of sICAM‐1 in vitro. Increased expression of ICAM‐1 by interferon‐γ and tumor necrosis factor α alone, and the further induction in combination with β‐estradiol may underlie an aspect of fibroblast dysfunction in SSc and the female predisposition to the disease. Copyright © 1994 American College of Rheumatology