Role of E- and P-selectin in migration of monocytes and polymorphonuclear leucocytes to cytokine and chemoattractant-induced cutaneous inflammation in the rat.

The contribution of E- and P-selectin in the rat to the migration of polymorphonuclear leucocytes (PMNL) and monocytes to acute dermal inflammation induced by a chemoattractant (C5ades Arg) or endothelial cell activating agents [lipopolysaccharide, tumour necrosis factor-alpha (TNF-alpha), alpha-thrombin and interferon-gamma] administered intradermally was investigated. Migration was quantitated using radiolabelled blood PMNL and monocytes and new, function-blocking monoclonal antibodies (mAbs) to rat E- and P-selectin were employed. Monocyte migration to inflamed skin was partially inhibited (40-75%) by P-selectin mAb with all stimuli tested, but not by anti-E-selectin. PMNL migration in response to all stimuli was also inhibited (50-75%) by blocking P-selectin, but in contrast to monocytes, PMNL accumulation was partially inhibited by mAb to E-selectin in alpha-thrombin and TNF-alpha lesions. When P-selectin was blocked by mAb, mAb to E-selectin significantly inhibited further (by 70-90%) both PMNL and monocyte accumulation in all lesions, indicating that both P- and E-selectin contribute to the migration of these leucocytes. Blocking L-selectin in addition to P- and E-selectin, had no effect on the remaining migration. Thus, optimal PMNL and monocyte migration to chemotactic factor- and cytokine-induced skin inflammation is P-selectin dependent. E-selectin becomes important, in most conditions used here, when P-selectin mediated recruitment is not operative. A selectin independent pathway likely mediates up to 20% of PMNL and monocyte migration to acute inflammation, at least in skin.