Strieter R M, Polverini P J, Arenberg D A, Kunkel S L
University of Michigan Medical School, Department of Internal Medicine (Division of Pulmonary and Critical Medicine, Ann Arbor 48109-0360, USA.
Shock. 1995 Sep;4(3):155-60. doi: 10.1097/00024382-199509000-00001.
The regulation of angiogenesis is fundamental to a variety of physiological and pathological processes. Although a number of factors have been identified that induce neovascularization, it is becoming increasingly apparent that endogenous angiostatic factors may play an important role in the regulation of angiogenesis during wound repair, chronic inflammation, and growth of solid tumors. In this review, we demonstrate that the CXC chemokine family of cytokines display disparate angiogenic activity depending upon the presence or absence of the ELR motif, a structural amino acid motif previously found to be important in receptor ligand binding on neutrophils. CXC chemokines containing the ELR motif are potent angiogenic factors, inducing both in vitro endothelial chemotaxis and in vivo corneal neovascularization. In contrast, the CXC chemokines that lack the ELR motif, PF4, IP-10, and MIG, not only fail to induce significant in vitro endothelial cell chemotaxis or in vivo corneal neovascularization, but are found to be potent angiostatic factors in the presence of CXC chemokines containing the ELR motif. These findings suggest that the CXC chemokine family can display disparate angiogenic activity that depends upon the presence or absence of the ELR motif. Furthermore, these studies support the notion that the net biological balance in the magnitude of expression of angiogenic and angiostatic CXC chemokines at either the site of wound repair or during tumorigenesis may be important in the regulation of net angiogenesis.
血管生成的调节对于多种生理和病理过程至关重要。尽管已经确定了许多诱导新血管形成的因素，但越来越明显的是，内源性血管生成抑制因子可能在伤口修复、慢性炎症和实体瘤生长过程中的血管生成调节中发挥重要作用。在本综述中，我们证明，CXC细胞因子家族的细胞因子根据ELR基序的存在与否表现出不同的血管生成活性，ELR基序是一种先前发现对中性粒细胞受体配体结合很重要的结构氨基酸基序。含有ELR基序的CXC趋化因子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。相反，缺乏ELR基序的CXC趋化因子PF4、IP-10和MIG不仅不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，而且在含有ELR基序的CXC趋化因子存在时被发现是有效的血管生成抑制因子。这些发现表明，CXC趋化因子家族可以根据ELR基序的存在与否表现出不同的血管生成活性。此外，这些研究支持这样一种观点，即在伤口修复部位或肿瘤发生过程中，血管生成和血管生成抑制性CXC趋化因子表达量的净生物学平衡可能在净血管生成的调节中起重要作用。
