Mac-1（CD11b/CD18）是主要的β2（CD18）整合素，介导人类中性粒细胞通过滑膜和成纤维细胞屏障迁移。

Mac-1 (CD11b/CD18) is the predominant beta 2 (CD18) integrin mediating human neutrophil migration through synovial and dermal fibroblast barriers.

作者信息

Gao J X, Issekutz A C

机构信息

Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.

出版信息

Immunology. 1996 Jul;88(3):463-70. doi: 10.1046/j.1365-2567.1996.d01-662.x.

DOI:10.1046/j.1365-2567.1996.d01-662.x

PMID:8774366

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1456357/

Abstract

Recently we reported that polymorphonuclear leucocyte (PMNL) migration in vitro through a barrier of human synovial fibroblasts (HSF) involves both beta 2 (CD18) and beta 1 (CD29) integrins on the PMNL. Here we investigated the role of the beta 2 integrin family members, lymphocyte function-associated (LFA)-1 (alpha L beta 2 or CD11a/CD18) and Mac-1 ( alpha M beta 2 or CD11b/CD18), in PMNL migration through HSF and human dermal fibroblast (HDF) monolayers. Treatment of PMNL with monoclonal antibody (mAb) to LFA-1 (anti-alpha L) did not inhibit PMNL migration through either monolayer in response to C5a. In contrast, mAb to Mac-1 (Cd11b) inhibited (by 30-40%) PMNL migration, and by virtually the same extent as mAb to the beta 1 integrin chain (CD18) (40% inhibition). Addition of mAb to LFA-1 to mAb to Mac-1 did not result in greater inhibition. This was in contrast to PMNL migration through human umbilical vein endothelium (HUVE) monolayers, where mAb to LFA-1 or to Mac-1 each partially inhibited PMNL transendothelial migration, and when these mAbs were combined, synergistic inhibition of migration was observed, reaching 90-95% inhibition. Intercellular adhesion molecule 1 (ICAM-1) was not required for Mac-1 mediated migration through HSF or HDF, because treatment of the fibroblasts with mAb R6.5 (F(ab)2) to ICAM-1, which blocks the Mac-1 binding site on ICAM-1, did not inhibit PMNL migration. An LFA-1-ICAM-1 mechanism of PMNL migration through HSF and HDF monolayers could be detected after treatment (4 hr) of the monolayers with TNF-alpha plus IFN-gamma, which upregulated ICAM-1 on the fibroblasts. The results demonstrate the beta 2 integrin dependent PMNL migration in connective tissue may involve primarily Mac-1, with little involvement of LFA-1 or ICAM-1, a situation in marked contrast to PMNL migration across endothelium. However, in inflammatory conditions in which TNF-alpha and/or IFN-gamma may be generated, a role for LFA-1-ICAM-1 may be induced.

摘要

最近我们报道，多形核白细胞（PMNL）在体外通过人滑膜成纤维细胞（HSF）屏障的迁移涉及PMNL上的β2（CD18）和β1（CD29）整合素。在此，我们研究了β2整合素家族成员，淋巴细胞功能相关抗原-1（LFA-1，αLβ2或CD11a/CD18）和巨噬细胞-1（Mac-1，αMβ2或CD11b/CD18）在PMNL通过HSF和人皮肤成纤维细胞（HDF）单层迁移中的作用。用抗LFA-1单克隆抗体（mAb）（抗αL）处理PMNL，并不抑制其响应C5a通过任一单层的迁移。相反，抗Mac-1（CD11b）mAb抑制（30%-40%）PMNL迁移，其抑制程度与抗β1整合素链（CD18）mAb几乎相同（40%抑制）。将抗LFA-1 mAb与抗Mac-1 mAb联合使用，并未导致更大程度的抑制。这与PMNL通过人脐静脉内皮细胞（HUVE）单层的迁移情况相反，在HUVE单层迁移中，抗LFA-1或抗Mac-1 mAb各自部分抑制PMNL跨内皮迁移，当将这些mAb联合使用时，观察到迁移的协同抑制，抑制率达到90%-95%。Mac-1介导的通过HSF或HDF的迁移不需要细胞间黏附分子1（ICAM-1），因为用抗ICAM-1的mAb R6.5（F(ab)2）处理成纤维细胞，该抗体可阻断ICAM-1上的Mac-1结合位点，但并不抑制PMNL迁移。在用肿瘤坏死因子-α（TNF-α）加干扰素-γ（IFN-γ）处理单层细胞（4小时）后，可检测到PMNL通过HSF和HDF单层迁移的LFA-1-ICAM-1机制，这会上调成纤维细胞上的ICAM-1。结果表明，在结缔组织中，β2整合素依赖性PMNL迁移可能主要涉及Mac-1，而LFA-1或ICAM-1参与较少，这种情况与PMNL跨内皮迁移形成鲜明对比。然而，在可能产生TNF-α和/或IFN-γ的炎症条件下，可能会诱导LFA-1-ICAM-1发挥作用。