Neutrophil beta 2-integrin upregulation is blocked by a p38 MAP kinase inhibitor

Tumor necrosis factor-alpha is known to upregulate the expression of surfac e adhesion molecules on polymorphonuclear leukocytes (PMNs). The purpose of this investigation was to study possible intracellular signaling pathways responsible for the upregulation of beta 2 integrins on normal human PMNs i nduced by TNF. We report that treatment with TNF (10 ng/ml) for 30 min resu lted in a significant increase in CD18 and MAC-1 surface expression (P < 0. 001). In addition, pretreatment with 15 mu M SB203580, a p38 MAP kinase inh ibitor, for 10 min significantly inhibited TNF upregulation of CD18 and MAC -1 (P < 0.0001). Pretreatment with either 15 mu M PD 98059, a p42/44 MAP ki nase inhibitor, or 5 mu M GO 6850, a protein kinase C inhibitor, had no sig nificant inhibitory effect. These data suggest that the TNF-induced upregul ation of beta 2 integrins is mediated specifically through the p38 MAP kina se pathway and not through the p42/44 MAP kinase or protein kinase C pathwa ys. (C) 2000 Academic Press.