Strieter R M, Polverini P J, Kunkel S L, Arenberg D A, Burdick M D, Kasper J, Dzuiba J, Van Damme J, Walz A, Marriott D
Department of Internal Medicine (Division of Pulmonary and Critical Medicine), University of Michigan Medical School, Ann Arbor 48109-0360, USA.
J Biol Chem. 1995 Nov 10;270(45):27348-57. doi: 10.1074/jbc.270.45.27348.
In this study, we demonstrate that the CXC family of chemokines displays disparate angiogenic activity depending upon the presence or absence of the ELR motif. CXC chemokines containing the ELR motif (ELR-CXC chemokines) were found to be potent angiogenic factors, inducing both in vitro endothelial chemotaxis and in vivo corneal neovascularization. In contrast, the CXC chemokines lacking the ELR motif, platelet factor 4, interferon gamma-inducible protein 10, and monokine induced by gamma-interferon, not only failed to induce significant in vitro endothelial cell chemotaxis or in vivo corneal neovascularization but were found to be potent angiostatic factors in the presence of either ELR-CXC chemokines or the unrelated angiogenic factor, basic fibroblast growth factor. Additionally, mutant interleukin-8 proteins lacking the ELR motif demonstrated potent angiostatic effects in the presence of either ELR-CXC chemokines or basic fibroblast growth factor. In contrast, a mutant of monokine induced by gamma-interferon containing the ELR motif was found to induce in vivo angiogenic activity. These findings suggest a functional role of the ELR motif in determining the angiogenic or angiostatic potential of CXC chemokines, supporting the hypothesis that the net biological balance between angiogenic and angiostatic CXC chemokines may play an important role in regulating overall angiogenesis.
在本研究中，我们证明趋化因子CXC家族根据ELR基序的有无表现出不同的血管生成活性。含有ELR基序的CXC趋化因子（ELR-CXC趋化因子）被发现是有效的血管生成因子，可诱导体外内皮细胞趋化和体内角膜新生血管形成。相比之下，缺乏ELR基序的CXC趋化因子、血小板因子4、γ干扰素诱导蛋白10和γ干扰素诱导的单核因子，不仅未能诱导显著的体外内皮细胞趋化或体内角膜新生血管形成，而且在存在ELR-CXC趋化因子或无关血管生成因子碱性成纤维细胞生长因子的情况下，被发现是有效的血管生成抑制因子。此外，缺乏ELR基序的突变白细胞介素-8蛋白在存在ELR-CXC趋化因子或碱性成纤维细胞生长因子的情况下表现出强大的血管生成抑制作用。相比之下，含有ELR基序的γ干扰素诱导的单核因子突变体被发现可诱导体内血管生成活性。这些发现表明ELR基序在决定CXC趋化因子的血管生成或血管生成抑制潜力方面具有功能作用，支持了血管生成和血管生成抑制CXC趋化因子之间的净生物学平衡可能在调节整体血管生成中起重要作用的假设。
