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

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Abstract
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‐&agr; (TNF‐&agr;), &agr;‐thrombin and interferon‐&ggr;] 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 &agr;‐thrombin and TNF‐&agr; 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.