Strieter Robert M, Belperio John A, Burdick Marie D, Keane Michael P
Division of Pulmonary, Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024-1922, USA.
Curr Drug Targets Inflamm Allergy. 2005 Feb;4(1):23-6. doi: 10.2174/1568010053622902.
The CXC chemokines are an unique family of cytokines known for their ability to behave in a disparate manner in the regulation of angiogenesis. The mechanisms for the different activity in regulating angiogenesis by members of this chemokine family is related to the following: 1) the presence or absence of the structural/functional motif (Glutamic acid-Leucine-Arginine; 'ELR' motif) that immediately precedes the first cysteine amino acid residue in the primary structure of these cytokines; 2) interferon-inducible gene expression; and 3) receptors that these chemokines use to mediate their biological activity. Members that contain the 'ELR' motif (ELR(+)) are potent promoters of angiogenesis, and mediate their angiogenic activity via binding and activating CXCR2 on endothelium. In contrast, members that are inducible by interferons and lack the ELR motif (ELR(-)) are potent inhibitors of angiogenesis, and bind to the alternatively splice variant of CXCR3, CXCR3B on endothelium. This review will discuss the biology of these angiogenic and angiostatic CXC chemokines, and discuss their disparate angiogenic activity in the context of a variety of chronic fibroproliferative disorders.
CXC趋化因子是一类独特的细胞因子，以其在血管生成调节中表现出的不同作用方式而闻名。该趋化因子家族成员在调节血管生成中具有不同活性的机制与以下因素有关：1）这些细胞因子一级结构中第一个半胱氨酸氨基酸残基之前是否存在结构/功能基序（谷氨酸-亮氨酸-精氨酸；“ELR”基序）；2）干扰素诱导的基因表达；3）这些趋化因子用于介导其生物学活性的受体。含有“ELR”基序（ELR(+)）的成员是血管生成的强效促进剂，通过结合并激活内皮细胞上的CXCR2来介导其血管生成活性。相反，受干扰素诱导且缺乏ELR基序（ELR(-)）的成员是血管生成的强效抑制剂，并与内皮细胞上CXCR3的可变剪接变体CXCR3B结合。本综述将讨论这些促血管生成和抑血管生成的CXC趋化因子的生物学特性，并在各种慢性纤维增生性疾病的背景下讨论它们不同的血管生成活性。
