Neutrophil beta2-integrin upregulation is blocked by a p38 MAP kinase inhibitor.

Tumor necrosis factor-alpha is known to upregulate the expression of surface adhesion molecules on polymorphonuclear leukocytes (PMNs). The purpose of this investigation was to study possible intracellular signaling pathways responsible for the upregulation of beta2 integrins on normal human PMNs induced by TNF. We report that treatment with TNF (10 ng/ml) for 30 min resulted in a significant increase in CD18 and MAC-1 surface expression (P < 0.001). In addition, pretreatment with 15 microM SB203580, a p38 MAP kinase inhibitor, for 10 min significantly inhibited TNF upregulation of CD18 and MAC-1 (P < 0.0001). Pretreatment with either 15 microM PD 98059, a p42/44 MAP kinase inhibitor, or 5 microM GO 6850, a protein kinase C inhibitor, had no significant inhibitory effect. These data suggest that the TNF-induced upregulation of beta2 integrins is mediated specifically through the p38 MAP kinase pathway and not through the p42/44 MAP kinase or protein kinase C pathways. Copyright 2000 Academic Press.