VLA-4 INTEGRIN CAN MEDIATE CD11 CD18-INDEPENDENT TRANSENDOTHELIAL MIGRATION OF HUMAN MONOCYTES
VLA-4 INTEGRIN CAN MEDIATE CD11 CD18-INDEPENDENT TRANSENDOTHELIAL MIGRATION OF HUMAN MONOCYTES
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DOI：
10.1172/jci116895
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发表时间：
1993-12-01
影响因子：
15.9
通讯作者：
ISSEKUTZ, AC
中科院分区：
文献类型：
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作者：
CHULUYAN, HE;ISSEKUTZ, AC
研究了人单核细胞响应趋化因子而穿过未激活和激活的人脐静脉内皮 (HUVE) 的迁移，并对所涉及的粘附分子进行了表征。由 C5a 诱导的血液单核细胞或 U937 细胞系来源的单核细胞穿过未激活的 HUVE 的迁移被单核细胞上 CD11/CD18 复合物的 CD18 的 mAb（R15.7 或 60.3）部分抑制（75%）。然而，当HUVE用IL-1α（0.1ng/ml）、TNF-α（100U/ml）或LPS（1ng/ml）预处理5小时时，C5a诱导的迁移不再受到抑制；即，迁移变得独立于 CD18。单核细胞不依赖于 CD18 的迁移被针对 VLA4 的 α4 或 β1 整合素链的单克隆抗体完全阻断。这种迁移也被针对血管细胞粘附分子 1 (VCAM-1) 的单克隆抗体部分抑制，该单克隆抗体是 HUVE 上 VLA4 的主要反受体，但不被针对 E-选择素或细胞间粘附分子 1 的单克隆抗体所抑制。针对 VLA4 的 α4 或 β1 链的单克隆抗体也可抑制跨“未激活”HUVE 的显着的 CD18 依赖性迁移，尽管针对 VCAM-1 的单克隆抗体在这些条件下没有抑制作用。最后，在 CD18 缺陷（白细胞粘附缺陷）患者的单核细胞中也观察到相当多的 VLA-4 依赖性跨内皮迁移至 C5a。这些结果表明（a）单核细胞趋化因子依赖性跨激活和未激活内皮细胞的迁移中存在一个主要的不依赖 CD18 的成分； (b) 单核细胞上的 VLA4 整合素在这种迁移中起主要作用； (c) 活化内皮上的 VCAM-1 在此过程中充当反受体，但 VLA4 的其他配体，尤其是未活化内皮上的 VLA4 配体也可能参与其中。
The migration of human monocytes across unactivated and activated human umbilical vein endothelium (HUVE) in response to chemotactic factors was studied, and the adhesion molecules involved were characterized. Migration of blood monocytes or U937 cell line-derived monocytes across unactivated HUVE induced by C5a, was partially inhibited (by 75%) by mAbs (R15.7 or 60.3) to CD18 of the CD11/CD18 complex on the monocyte. However, when the HUVE was pretreated for 5 h with IL-1alpha (0.1 ng/ml), TNF-alpha (100 U/ml), or LPS (1 ng/ml), migration induced by C5a was no longer inhibited; i.e., migration became CD18 independent. The monocyte CD18-independent migration was completely blocked by mAbs against alpha4 or beta1 integrin chains of VLA4. This migration was also partially inhibited by mAbs against vascular cell adhesion molecule-1 (VCAM-1), a major counter-receptor on HUVE for VLA4, but not by mAbs to E-selectin or intercellular adhesion molecule-1. The significant CD18-independent migration across ''unactivated'' HUVE was also inhibited by mAbs against alpha4 or beta1 chains of VLA4, although mAbs against VCAM-1 did not inhibit under these conditions. Finally, considerable VLA-4-dependent transendothelial migration to C5a was also observed with monocytes from a patient with CD18 deficiency (leukocyte adhesion deficiency). These results suggest that (a) there is a major CD18-independent component in monocyte chemotactic factor-dependent migration across activated and unactivated endothelium; (b) that VLA4 integrin on the monocyte has a major role in this migration; and (c) that VCAM-1 on activated endothelium functions as a counter-receptor in this process, but other ligands for VLA4, especially on unactivated endothelium, may also be involved.