Regulation of ICAM-1 expression in mouse macrophages

In a mouse model of silica (SI) induced Lung injury, SI exposure increases expression of intercellular adhesion molecule-1 (ICAM-1) on lung (alveolar/interstitial) macrophages and alveolar type II epithelial cells. To investigate the regulation of SI induced ICAM-1 expression on mouse macrophages, freshly isolated macrophages (alveolar, peritoneal) and macrophage cell lines (MH-S, RAW 264.7) were evaluated for ICAM-1 expression elicited by the particle silica (alpha quartz; 20 mu g/ml; 6 mu g/cm(2)) or the inflammatory cytokine, TNF alpha (20 ng/ml). TNF alpha significantly increased ICAM-1 expression in all cell types whereas SI elicited an increase in peritoneal macrophages (PM) and the cell line, MH-S. This pattern of increased expression was confirmed by immunocytochemistry. To investigate the regulation of ICAM-1 expression, PM were incubated with SI, TNF alpha or media concomitantly with anti-TNF alpha antibody, the antioxidant, NAG, or the iNOS synthase inhibitor, L-NAME. Both anti-TNF alpha and NAG, but not L-NAME, inhibited elicited (TNF alpha, SI) as well as constitutive (media) ICAM-1 expression. These data demonstrate that both inflammatory cytokines and inorganic particles can increase ICAM-1 expression on mouse macrophages and that this expression is mediated, in part, by TNF alpha and reactive oxygen species.