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. Beta-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-gamma and tumor necrosis factor alpha alone, and the further induction in combination with beta-estradiol may underlie an aspect of fibroblast dysfunction in SSc and the female predisposition to the disease.
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. Beta-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-gamma and tumor necrosis factor alpha alone, and the further induction in combination with beta-estradiol may underlie an aspect of fibroblast dysfunction in SSc and the female predisposition to the disease.
Authors: Ann E Brannigan; R William G Watson; David Beddy; Hilary Hurley; John M Fitzpatrick; P Ronan O'Connell Journal: Ann Surg Date: 2002-04 Impact factor: 12.969