Dual inhibition of VLA-4 and LFA-1 maximally inhibits cutaneous delayed-type hypersensitivity-induced inflammation.

Dual inhibition of VLA-4 and LFA-1 maximally inhibits cutaneous delayed-type hypersensitivity-induced inflammation.
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VLA-4 和 LFA-1 的双重抑制可最大程度地抑制皮肤迟发型超敏反应诱发的炎症。

DOI:
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发表时间:
1993
影响因子:
6
通讯作者:
T. Issekutz
T. Issekutz
中科院分区:
医学2区
文献类型:
--
作者:
T. Issekutz

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淋巴细胞表达介导内皮细胞粘附并控制 T 细胞迁移至炎症部位的表面受体。淋巴细胞 VLA-4 和 LFA-1 介导与细胞因子激活的内皮细胞的粘附,但这些分子对体内迁移和淋巴细胞介导的炎症的贡献尚不清楚。在这里,我们表明,VLA-4 和 LFA-1 不仅有助于淋巴细胞粘附,而且有助于大鼠体内淋巴细胞迁移,并且当两个整合素被阻断时,观察到几乎完全抑制淋巴细胞积累。此外,用抗VLA-4或抗LFA-1观察到对迟发型超敏反应诱导的炎症的抑制(通过皮肤硬结和纤维蛋白沉积来量化),但通过阻断两种整联蛋白观察到更强的抑制作用。因此,在某些类型的 T 细胞介导的炎症中,需要双重抑制 VLA-4 和 LFA-1 途径才能获得最大的抗炎作用。
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.
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