TUMOR-NECROSIS-FACTOR-ALPHA REGULATES INVIVO INTRAPULMONARY EXPRESSION OF ICAM-1

Lung injury following deposition of IgG immune complexes is neutrophil -dependent and requires both tumor necrosis factor alpha(TNFalpha) and CD18. In the current studies, we have evaluated the relationship betw een TNFalpha and expression of intracellular adhesion molecule-1 (ICAM -1) in vitro and in vivo. In both rat pulmonary artery endothelial cel ls and human umbilical vein endothelial cells, TVFalpha induced an ear ly (within 60 minutes) increase in ICAM-1 expression, followed by a pe ak al 6 to 8 hours with relatively stable expression al 24 hours. Expr ession of E-selectin did not show the early phase (within 60 minutes) of up-regulation, peaked at 4 hours, and then declined thereafter. Usi ng a radioimmunochemical assay in vivo, it was demonstrated that intra pulmonary deposition of IgG immune complexes caused a progressive incr ease in ICAM-1 expression in lung over an 8-hour period. In animals pr etreated with antibody to TNFalpha, the intrapulmonary expression of I CAM-1 was significantly reduced. These results were confirmed by immun operoxidase analysis of lung tissue. It las also shown that airway ins tillation of TNFalpha caused up-regulation of ICAM-1 in lung. These da ta support the concept that deposition of IgG immune complexes in lung induces intrapulmonary up-regulation of ICAM-1 in a manner that is TN Falpha-dependent.