Morzycki W, Issekutz A C
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
Immunology. 1991 Sep;74(1):107-13.
Interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) both induce polymorphonuclear leucocyte (PMNL) infiltration into tissues and they have a synergistic action in this respect. We and others have observed that IL-1 alpha and TNF-alpha induce 51Cr-labelled PMNL migration across monolayers of umbilical vein endothelium via an endothelial cell-dependent mechanism. Here we investigated the interaction of PMNL with fibroblasts, since PMNL probably encounter such cells in many tissues once they traverse the vascular wall. TNF-alpha, but not IL-1 alpha, was found to activate fibroblast monolayers, grown on polycarbonate filters, to stimulate PMNL transfibroblast migration. This was a time- and fibroblast-dependent process which required fibroblast protein synthesis, as indicated by inhibition with cycloheximide. The effect of TNF-alpha was not related to fibroblast chemotactic factor production (primarily IL-8), or to ICAM-1 up-regulation, since IL-1 was as active as TNF-alpha in this respect, without activating fibroblasts to support PMNL transfibroblast migration. Antiserum to IL-8, present during the assay, did not inhibit PMNL migration across the monolayers. The PMNL migration was highly dependent on the function of both CD11a (LFA-1) and CD11b (MAC-1) PMNL adhesion molecules, since monoclonal antibodies to either inhibited migration by about 80%. The results suggest a distinct activation by TNF-alpha of fibroblasts to facilitate PMNL migration through fibroblast barriers. These findings may in part account for the synergistic action of IL-1 and TNF-alpha in inducing extravascular accumulation of PMNL during inflammation.
白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α）均可诱导多形核白细胞（PMNL）浸润至组织中，且在这方面它们具有协同作用。我们和其他人观察到，IL-1α和TNF-α通过内皮细胞依赖性机制诱导51Cr标记的PMNL跨脐静脉内皮单层迁移。在此，我们研究了PMNL与成纤维细胞的相互作用，因为PMNL一旦穿过血管壁，很可能在许多组织中会遇到此类细胞。发现TNF-α而非IL-1α可激活生长在聚碳酸酯滤膜上的成纤维细胞单层，以刺激PMNL跨成纤维细胞迁移。这是一个时间和成纤维细胞依赖性过程，需要成纤维细胞蛋白质合成，环己酰亚胺抑制作用表明了这一点。TNF-α的作用与成纤维细胞趋化因子产生（主要是IL-8）或ICAM-1上调无关，因为IL-1在这方面与TNF-α一样活跃，但不会激活成纤维细胞来支持PMNL跨成纤维细胞迁移。检测过程中存在的抗IL-8抗血清不会抑制PMNL跨单层迁移。PMNL迁移高度依赖于CD11a（LFA-1）和CD11b（MAC-1）这两种PMNL黏附分子的功能，因为针对其中任何一种的单克隆抗体均可抑制迁移约80%。结果表明TNF-α对成纤维细胞有独特的激活作用，以促进PMNL通过成纤维细胞屏障迁移。这些发现可能部分解释了IL-1和TNF-α在炎症过程中诱导PMNL血管外积聚的协同作用。
