Issekutz T B
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
Am J Pathol. 1993 Nov;143(5):1286-93.
Lymphocytes express surface receptors that mediate adhesion to endothelial cells and control T cell migration into inflammatory sites. Lymphocyte VLA-4 and LFA-1 mediate adhesion to cytokine-activated endothelium, but the contribution of these molecules to in vivo migration and lymphocyte mediated inflammation is not clear. Here we show that both VLA-4 and LFA-1 contribute to not only lymphocyte adhesion but to in vivo lymphocyte migration in the rat and that nearly complete inhibition of lymphocyte accumulation is observed when both integrins are blocked. Furthermore, inhibition of delayed-type hypersensitivity-induced inflammation, as quantified by skin induration and fibrin deposition, is observed with either anti-VLA-4 or anti-LFA-1, but much stronger inhibition is observed with a blockade of both integrins. Thus, dual inhibition of the VLA-4 and LFA-1 pathways is required for a maximal anti-inflammatory effect in some types of T cell-mediated inflammation.
淋巴细胞表达介导与内皮细胞黏附并控制T细胞迁移至炎症部位的表面受体。淋巴细胞的VLA-4和LFA-1介导与细胞因子激活的内皮细胞的黏附，但这些分子对体内迁移和淋巴细胞介导的炎症的作用尚不清楚。在此我们表明，VLA-4和LFA-1不仅有助于淋巴细胞黏附，而且对大鼠体内淋巴细胞迁移也有作用，并且当两种整合素均被阻断时，可观察到淋巴细胞聚集几乎完全受到抑制。此外，用抗VLA-4或抗LFA-1均可观察到迟发型超敏反应诱导的炎症受到抑制，这通过皮肤硬结和纤维蛋白沉积来量化，但当两种整合素均被阻断时，观察到的抑制作用更强。因此，在某些类型的T细胞介导的炎症中，要实现最大的抗炎效果，需要对VLA-4和LFA-1途径进行双重抑制。
