人类多形核白细胞通过滑膜成纤维细胞屏障的迁移是由β2（CD11/CD18）整合素以及β1（CD29）整合素VLA - 5和VLA - 6介导的。

Migration of human polymorphonuclear leukocytes through a synovial fibroblast barrier is mediated by both beta 2 (CD11/CD18) integrins and the beta 1 (CD29) integrins VLA-5 and VLA-6.

作者信息

Gao J X, Wilkins J, Issekutz A C

机构信息

Department of Pediatrics, Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.

出版信息

Cell Immunol. 1995 Jul;163(2):178-86. doi: 10.1006/cimm.1995.1114.

DOI:10.1006/cimm.1995.1114

PMID:7541723

Abstract

Polymorphonuclear leukocytes (PMNL) accumulate in joint fluid in inflammatory arthritides. We investigated the molecular mechanisms required for PMNL migration through a barrier of human synovial fibroblasts (HSF) grown on microporous filters, as a model of PMNL migration through synovial connective tissue and compared this process with PMNL migration through human dermal fibroblast (HDF) barriers and through human umbilical vein endothelium (HUVE). A small amount of PMNL migration occurred spontaneously only through the synovial fibroblast/filter unit (6-10%). Migration markedly increased through all cell monolayers when the chemotactic factors C5a, IL-8, or zymosan-activated plasma (containing C5adesArg) were added to form a chemotactic gradient. The migration induced by C5a, IL-8, or C5adesArg across HSF was partially inhibited (25-76% depending on stimulus) by mAb to CD18 (beta 2 integrin). The CD18-independent migration induced by IL-8 or C5adesArg was almost completely inhibited by mAbs to beta 1 integrin, but with C5a, inhibition by mAb to beta 1 integrin was only partial (40-50%). Inhibition by mAb to beta 1 integrin required treatment of the PMNL, but not the HSF and was only observed when the function of CD11/CD18 on PMNL was also blocked by a mAb. Treatment of PMNL with mAb to alpha 5 (VLA-5) plus alpha 6 (VLA-6) in combination, was required to inhibit CD18-independent migration through HSF to the degree observed with mAb to beta 1 integrin. There was no qualitative difference in the mechanisms utilized by PMNL for migration through HSF or HDF in response to chemotactic factors. In contrast, PMNL migration across HUVE was almost completely CD18-dependent (85%) with no role for beta 1 integrins. The results suggest that (a) PMNL migration through HSF in response to chemotactic factors utilizes both CD11/CD18 and beta 1 (CD29) integrins; (b) the VLA-5 and VLA-6 members of beta 1 integrins are involved in mediating migration; and (c) PMNL utilize similar mechanisms for migration through HSF and HDF, which are distinct from migration through HUVE.

摘要

多形核白细胞（PMNL）在炎症性关节炎的关节液中积聚。我们研究了PMNL通过生长在微孔滤膜上的人滑膜成纤维细胞（HSF）屏障迁移所需的分子机制，以此作为PMNL通过滑膜结缔组织迁移的模型，并将此过程与PMNL通过人皮肤成纤维细胞（HDF）屏障和人脐静脉内皮细胞（HUVE）的迁移进行比较。只有少量PMNL仅通过滑膜成纤维细胞/滤膜单元自发迁移（6 - 10%）。当加入趋化因子C5a、IL - 8或酵母聚糖激活的血浆（含C5adesArg）以形成趋化梯度时，通过所有细胞单层的迁移显著增加。抗CD18（β2整合素）单克隆抗体可部分抑制（取决于刺激因素，抑制率为25 - 76%）C5a、IL - 8或C5adesArg诱导的PMNL跨HSF迁移。IL - 8或C5adesArg诱导的不依赖CD18的迁移几乎完全被抗β1整合素单克隆抗体抑制，但对于C5a，抗β1整合素单克隆抗体的抑制作用仅为部分（40 - 50%）。抗β1整合素单克隆抗体的抑制作用需要对PMNL进行处理，而不是对HSF进行处理，并且只有当PMNL上的CD11/CD18功能也被单克隆抗体阻断时才会观察到。用抗α5（VLA - 5）加α6（VLA - 6）的单克隆抗体联合处理PMNL，才能将不依赖CD18的通过HSF的迁移抑制到与抗β1整合素单克隆抗体观察到的程度相同。PMNL在趋化因子作用下通过HSF或HDF迁移所利用的机制没有质的差异。相比之下，PMNL跨HUVE的迁移几乎完全依赖CD18（85%），β1整合素不发挥作用。结果表明：（a）PMNL在趋化因子作用下通过HSF迁移同时利用CD11/CD18和β1（CD29）整合素；（b）β1整合素的VLA - 5和VLA - 6成员参与介导迁移；（c）PMNL通过HSF和HDF迁移利用相似的机制，这与通过HUVE的迁移不同。