Suppr超能文献

CD18和VLA - 4在抗肾小球基底膜肾炎中白细胞迁移/激活过程中的不同作用。

Differing roles of CD18 and VLA-4 in leukocyte migration/activation during anti-GBM nephritis.

作者信息

Wu X, Tiwari A K, Issekutz T B, Lefkowith J B

机构信息

Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

出版信息

Kidney Int. 1996 Aug;50(2):462-72. doi: 10.1038/ki.1996.337.

Abstract

The mechanisms underlying leukocyte migration into inflamed glomeruli and their in situ activation are incompletely understood. We addressed this issue by investigating the effects of monoclonal antibodies (mAbs) to CD18 and VLA-4 on these process in the heterologous phase of anti-glomerular basement membrane (GBM) nephritis in rat. Anti-CD18 mAb substantially attenuated neutrophil (PMN) migration into glomeruli and the accompanying proteinuria which is a function of in situ leukocyte activation (ca. 60%). Anti-VLA-4 mAb modestly inhibited PMN migration (ca. 20%) and had no significant effect on proteinuria. Combination of both mAbs was no more effective than anti-CD18 mAb alone. Despite continued mAb blockade of CD18 or VLA-4 (or both), macrophage (M phi) migration following PMN influx was unaltered. However, combined CD18/VLA-4 mAbs diminished the proteinuria associated with M phi influx (ca. 50%). Abrogation of the acute influx of PMNs in this model (via complement depletion or anti-PMN antibody) did not diminish the following influx of M phi s, although the associated proteinuria was abolished. In this context, M phi migration was substantially decreased by anti-VLA-4 mAb (ca. 50%), but not anti-CD18 mAb (either alone or with anti-VLA-4 mAb). In sum, leukocyte migration and activation in the heterologous phase of anti-GBM nephritis are dependent on CD18 and VLA-4, although to varying degrees depending on the leukocyte subtype and the presence of prior inflammation. Nonetheless, a significant component of both PMN and M phi migration/activation is CD18/VLA-4 independent.

摘要

白细胞迁移至炎症性肾小球的机制及其原位激活机制尚未完全明确。我们通过研究抗CD18和VLA-4单克隆抗体(mAb)对大鼠抗肾小球基底膜(GBM)肾炎异源期这些过程的影响来解决这一问题。抗CD18 mAb显著减弱了中性粒细胞(PMN)向肾小球的迁移以及伴随的蛋白尿,蛋白尿是原位白细胞激活的一种表现(约60%)。抗VLA-4 mAb适度抑制PMN迁移(约20%),对蛋白尿无显著影响。两种mAb联合使用并不比单独使用抗CD18 mAb更有效。尽管持续用mAb阻断CD18或VLA-4(或两者),PMN流入后巨噬细胞(M phi)的迁移未改变。然而,联合使用CD18/VLA-4 mAb减少了与M phi流入相关的蛋白尿(约50%)。在该模型中,消除PMN的急性流入(通过补体耗竭或抗PMN抗体)并没有减少随后M phi的流入,尽管相关的蛋白尿被消除了。在此背景下,抗VLA-4 mAb使M phi迁移显著减少(约50%),但抗CD18 mAb(单独或与抗VLA-4 mAb联合使用)则无此作用。总之,抗GBM肾炎异源期白细胞的迁移和激活依赖于CD18和VLA-4,尽管程度因白细胞亚型和先前炎症的存在而异。尽管如此,PMN和M phi迁移/激活的一个重要部分是不依赖于CD18/VLA-4的。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验