Shang X Z, Lang B J, Issekutz A C
Department of Pediatrics, Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
J Immunol. 1998 Jan 1;160(1):467-74.
Monocytes migrate through vascular endothelium, and then in connective tissue. As a model of this process, we investigated adhesion molecules involved in monocyte migration through HUVEC and a barrier of human synovial fibroblasts (HSF). Minimal spontaneous monocyte migration (6-7%) occurred through either cell barrier, but this increased markedly (27-35% of added monocytes) when a C5a chemotactic gradient was present. Migration across unstimulated HUVEC was partially inhibited (40%) by mAb to CD18 (beta2 integrin) and completely blocked by anti-CD18 plus anti-alpha4 (CD49d; very late Ag-4 (VLA-4)) mAbs. In contrast, migration across HSF induced by C5a or monocyte chemoattractant protein-1 was not inhibited by mAb to CD18 and was only partially inhibited (33%) in combination with anti-alpha4 mAb. The CD18- and VLA-4-independent migration across HSF was completely inhibited by mAb to alpha5 of VLA-5. The inhibitory effect of mAbs to VLA-4 and VLA-5 was on the monocyte and required blockade of CD11/CD18 to be observed. In contrast to HSF, no role for VLA-5 in monocyte transendothelial migration was detected. Both HSF and IL-1-stimulated HUVEC expressed vascular cell adhesion molecule-1 (VCAM-1). However, VLA-4-mediated monocyte migration across HSF was only partially dependent on VCAM-1, in contrast to transendothelial migration, which was completely blocked by anti-VCAM-1 mAbs. In conclusion, unlike transendothelial migration, for which VLA-4 is the alternative mechanism to CD11/CD18 on monocytes, both VLA-4 and VLA-5 can mediate monocyte migration through fibroblast barriers. In addition to VCAM-1, other ligand(s) on HSF are also involved in the VLA-4-mediated migration.
单核细胞穿过血管内皮，然后进入结缔组织。作为这一过程的模型，我们研究了参与单核细胞通过人脐静脉内皮细胞（HUVEC）和人滑膜成纤维细胞（HSF）屏障迁移的黏附分子。通过任何一种细胞屏障的单核细胞自发迁移极少（6 - 7%），但当存在C5a趋化梯度时，这种迁移显著增加（占添加单核细胞的27 - 35%）。穿过未刺激的HUVEC的迁移被抗CD18（β2整合素）单克隆抗体部分抑制（40%），并被抗CD18加抗α4（CD49d；极迟抗原-4（VLA - 4））单克隆抗体完全阻断。相比之下，C5a或单核细胞趋化蛋白-1诱导的穿过HSF的迁移不被抗CD18单克隆抗体抑制，仅与抗α4单克隆抗体联合时被部分抑制（33%）。穿过HSF的不依赖CD18和VLA - 4的迁移被抗VLA - 5的α5单克隆抗体完全抑制。抗VLA - 4和VLA - 5单克隆抗体的抑制作用作用于单核细胞，且需要观察到CD11/CD18被阻断。与HSF不同，未检测到VLA - 5在单核细胞跨内皮迁移中的作用。HSF和IL - 1刺激的HUVEC均表达血管细胞黏附分子-1（VCAM - 1）。然而，与被抗VCAM - 1单克隆抗体完全阻断的跨内皮迁移不同，VLA - 4介导的单核细胞穿过HSF的迁移仅部分依赖于VCAM - 1。总之，与跨内皮迁移不同，对于跨内皮迁移VLA - 4是单核细胞上CD11/CD18的替代机制，而VLA - 4和VLA - 5均可介导单核细胞穿过成纤维细胞屏障的迁移。除了VCAM - 1，HSF上的其他配体也参与VLA - 4介导的迁移。
