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 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.


CONCLUSIONS
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.
Shi-Wen
X
X
Royal Free Hospital Medical School, London, UK.
Panesar
M
M
Vancheeswaran
R
R
Mason
J
J
Haskard
D
D
Black
C
C
Olsen
I
I
Abraham
D
D
D015703:Antigens, CD / Q000378:metabolism*; D018968:CD58 Antigens; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000473:pathology; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015703:Antigens, CD; D018968:CD58 Antigens; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D004958:Estradiol; D007371:Interferon-gamma