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, 51Cr‐labeled T lymphocytes migrated to lesions induced by IFN‐γ and tumor necrosis factor (TNF)‐α, and in even greater numbers to the combination of IFN‐γ + TNF‐α, and to sites injected with concanavalin A (Con A). In E‐selectin mAb‐treated and in E‐selectin‐deficient mice, IFN‐γ‐, IFN‐γ + TNF‐α‐ and Con A‐induced T cell accumulation was inhibited by 45–65%, but TNF‐α‐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.