Loike J D, el Khoury J, Cao L, Richards C P, Rascoff H, Mandeville J T, Maxfield F R, Silverstein S C
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
J Exp Med. 1995 May 1;181(5):1763-72. doi: 10.1084/jem.181.5.1763.
We have examined the capacity of four different chemoattractants/cytokines to promote directed migration of polymorphonuclear leukocytes (PMN) through three-dimensional gels composed of extracellular matrix proteins. About 20% of PMN migrated through fibrin gels and plasma clots in response to a gradient of interleukin 8 (IL-8) or leukotriene B4 (LTB4). In contrast, < 0.3% of PMN migrated through fibrin gels in response to a gradient of tumor necrosis factor alpha (TNF) or formyl-methionyl-leucyl-phenylalanine (FMLP). All four chemoattractants stimulated PMN to migrate through gels composed of collagen IV or of basement membrane proteins (Matrigel), or through filters to which fibronectin or fibrinogen had been adsorbed. PMN stimulated with TNF or FMLP adhered and formed zones of close apposition to fibrin, as measured by the exclusion of a 10-kD rhodamine-polyethylene glycol probe from the contact zones between PMN and the underlying fibrin gel. By this measure, IL-8- or LTB4-treated PMN adhered loosely to fibrin, since 10 kD rhodamine-polyethylene glycol permeated into the contact zones between these cells and the underlying fibrin gel. PMN stimulated with FMLP and IL-8, or FMLP and LTB4, exhibited very little migration through fibrin gels, and three times as many of these cells excluded 10 kD rhodamine-polyethylene glycol from their zones of contact with fibrin as PMN stimulated with IL-8 or LTB4 alone. These results show that PMN chemotaxis is regulated by both the nature of the chemoattractant and the composition of the extracellular matrix; they suggest that certain combinations of chemoattractants and matrix proteins may limit leukocyte movements and promote their localization in specific tissues in vivo.
我们研究了四种不同的趋化因子/细胞因子促使多形核白细胞（PMN）通过由细胞外基质蛋白构成的三维凝胶进行定向迁移的能力。约20%的PMN在白细胞介素8（IL-8）或白三烯B4（LTB4）梯度作用下穿过纤维蛋白凝胶和血浆凝块。相比之下，在肿瘤坏死因子α（TNF）或甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）梯度作用下，<0.3%的PMN穿过纤维蛋白凝胶。所有这四种趋化因子均刺激PMN穿过由IV型胶原或基底膜蛋白（基质胶）构成的凝胶，或穿过吸附有纤连蛋白或纤维蛋白原的滤膜。用TNF或FMLP刺激的PMN黏附并与纤维蛋白形成紧密贴附区，这可通过从PMN与下方纤维蛋白凝胶之间的接触区排除10-kD罗丹明-聚乙二醇探针来测定。通过这种方法测定，用IL-8或LTB4处理的PMN与纤维蛋白松散黏附，因为10 kD罗丹明-聚乙二醇渗透到这些细胞与下方纤维蛋白凝胶之间的接触区。用FMLP和IL-8或FMLP和LTB4刺激的PMN在纤维蛋白凝胶中迁移极少，并且与单独用IL-8或LTB4刺激的PMN相比，这些细胞中有三倍之多的细胞在其与纤维蛋白的接触区排除了10 kD罗丹明-聚乙二醇。这些结果表明，PMN趋化性受趋化因子的性质和细胞外基质的组成两者调节；它们提示趋化因子和基质蛋白的某些组合可能限制白细胞运动并促进其在体内特定组织中的定位。
