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
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
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DOI：
10.1006/cimm.1995.1114
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发表时间：
1995-07-01
影响因子：
4.3
通讯作者：
ISSEKUTZ, AC
中科院分区：
文献类型：
--
作者：
GAO, JX;WILKINS, J;ISSEKUTZ, AC
多形核白细胞（PMNL）在炎性关节炎的关节液中积聚。我们研究了PMNL迁移通过微孔过滤器上生长的人滑膜成纤维细胞（HSF）屏障所需的分子机制，作为PMNL迁移通过滑膜结缔组织的模型，并将此过程与PMNL迁移通过人真皮成纤维细胞（HDF）屏障和通过人脐静脉内皮细胞（HUVE）进行比较。少量PMNL仅通过滑膜成纤维细胞/滤器单位自发迁移（6-10%）。当加入趋化因子C5 a、IL-8或酵母聚糖激活的血浆（含C5 a（desArg））形成趋化梯度时，所有细胞单层的迁移显著增加。C5 a、IL-8或C5 a（des-Arg）Arg诱导的跨HSF的迁移被抗CD 18（β（2）整联蛋白）的mAb部分抑制（25-76%，取决于刺激）。针对B-1整联蛋白的mAb几乎完全抑制IL-8或C5 a（desArg）诱导的CD 18非依赖性迁移，但对于C5 a，mAb对B-1整联蛋白的抑制仅为部分（40-50%）。mAb对β（1）整合素的抑制需要PMNL的治疗，但不需要HSF，并且仅在PMNL上的CD 11/CD 18功能也被mAb阻断时观察到。需要用α 5（VLA-5）和α 6（VLA-6）的mAb联合治疗PMNL，以抑制CD 18非依赖性通过HSF的迁移，达到用β 1整联蛋白的mAb观察到的程度。PMNL通过HSF或HDF迁移以响应趋化因子的机制没有质的差异。相比之下，PMNL通过HUVE的迁移几乎完全依赖于CD 18（85%），而β（1）整合素没有作用。结果表明：（a）PMNL通过HSF迁移是对趋化因子的反应，利用了CD 11/CD 18和β（1）（CD 29）整联蛋白;（B）β（1）整联蛋白的VLA-5和VLA-6成员参与介导迁移;（c）PMNL通过HSF和HDF迁移的机制相似，与通过HUVE迁移不同。(C)出版社：Academic Press
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 C5a(desArg)) were added to form a chemotactic gradient. The migration induced by C5a, IL-8, or C5a(des-Arg) Arg 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 C5a(desArg) was almost completely inhibited by mAbs to B-1 integrin, but with C5a, inhibition by mAb to B-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. (C) 1995 Academic Press, Inc.