Differential role of E-selectin and P-selectin in T lymphocyte migration to cutaneous inflammatory reactions induced by cytokines

E-selectin and P-selectin are thought to be important in the infiltration of T lymphocytes in inflammation, but their role in cytokine-induced cutaneous inflammatory reactions has not been examined. A technique for quantifying labeled T lymphocyte migration to cytokine-induced dermal inflammation in mice was developed. After i.v. injection, (51)Cr-labeled T lymphocytes migrated to lesions induced by IFN-gamma and tumor necrosis factor (TNF)-alpha, and in even greater numbers to the combination of IFN-gamma + TNF-alpha, and to sites injected with concanavalin A (Con A). In E-selectin mAb-treated and in E-selectin-deficient mice, IFN-gamma-, IFN-gamma + TNF-alpha- and Con A-induced T cell accumulation was inhibited by 45-65%, but TNF-alpha-induced infiltration was unaffected. In P-selectin mAb-treated and P-selectin-deficient mice, T cell accumulation remained unchanged in most of the lesions. Combined, E-selectin and P-selectin mAb treatment inhibited T cell accumulation in all four types of reactions, and significantly more than E-selectin blockade alone in migration to Con A. Results in E-selectin- and P-selectin-deficient mice confirmed these observations, and demonstrated strain-dependent differences in the contributions of the two selectins. In conclusion, T cells migrating to dermal inflammatory reactions utilize both E-selectin and P-selectin, but alternate adhesion pathways also contribute, since blocking both endothelial selectins does not abolish T cell migration. P-selectin plays a less important role than E-selectin, since blocking E-selectin, but not P-selectin, alone decreased T cell accumulation. The relative contribution of the selectins varies depending on the initiating inflammatory stimulus and the genetic background.