Differential role of E-selectin and P-selectin in T lymphocyte migration to cutaneous inflammatory reactions induced by cytokines
Differential role of E-selectin and P-selectin in T lymphocyte migration to cutaneous inflammatory reactions induced by cytokines
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DOI：
10.1093/intimm/dxf045
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发表时间：
2002-07-01
影响因子：
4.4
通讯作者：
Issekutz, TB
中科院分区：
文献类型：
--
作者：
Kulidjian, AA;Issekutz, AC;Issekutz, TB
E-选择素和P-选择素被认为在炎症中T淋巴细胞的渗透中起重要作用，但它们在细胞因子诱导的皮肤炎症反应中的作用尚未被研究。建立了一种定量标记T淋巴细胞向细胞因子诱导的小鼠皮肤炎症迁移的技术。静脉注射后。注射后，Cr-51标记的T淋巴细胞迁移到干扰素-γ和肿瘤坏死因子-α诱导的损伤处，甚至更多迁移到干扰素-γ和肿瘤坏死因子-α的联合作用下，以及刀豆蛋白A(ConA)注射的部位。在E-选择素单抗治疗和E-选择素缺陷小鼠中，干扰素-γ、干扰素-γ+肿瘤坏死因子-α和刀豆蛋白A诱导的T细胞聚集被抑制45-65%，但不影响肿瘤坏死因子-α诱导的T细胞浸润。在P-选择素单抗治疗和P-选择素缺陷小鼠中，T细胞聚集在大多数皮损中保持不变。联合应用E-选择素和P-选择素mAb可抑制T细胞在所有四种反应中的聚集，在向ConA迁移的过程中，E-选择素和P-选择素单抗的抑制作用显著高于E-选择素和P-选择素的单独阻断。总而言之，迁移到真皮炎症反应的T细胞利用E-选择素和P-选择素，但替代的黏附途径也起作用，因为阻断这两种内皮选择素并不能消除T细胞的迁移。P-选择素的作用不如E-选择素重要，因为单独阻断E-选择素而不是P-选择素会减少T细胞的积聚。选择素的相对贡献取决于启动炎症刺激和遗传背景。
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, Cr-51-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.