Crosstalk between inflammation and angiogenesis

炎症和血管生成之间的串扰

• 批准号: 7291947
• 负责人: Triantafyllos Chavakis
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7291947
• 关键词: Crosstalk; between; inflammation; angiogenesis

Angiogenesis, the development and growth of new blood vessels, is important for organ development, wound healing and various pathological conditions such as tumor growth or proliferative retinopathies. Neovascularization depends on integrin-mediated adhesive contacts of the endothelial cells with the extracellular matrix as well as on the function of growth factors. There is emerging evidence that inflammatory cells, and particularly neutrophils, regulate endothelial cell functions related to angiogenesis. The participation of inflammatory cells in angiogenesis may depend on the biological context. Both pro-angiogenic and anti-angiogenic activities of neutrophils have been described. Neutrophils are a source of growth factors and proteases. However, neutrophil can generate the anti-angiogenic factors angiostatin and alpha-defensin. 1) We could show that alpha-defensins form a ternary complex with fibronectin (FN) and alpha5beta1-integrin and transform the FN-alpha5beta1-integrin interaction to one that does not promote endothelial cell adhesion. alpha-defensins thereby interfered with endothelial cell functions related to angiogenesis in vitro and in vivo. 2) The anti-angiogenic factor angiostatin was identified as a ligand of the leukocyte beta2-integrin Mac-1. Angiostatin was thereby found to exert an anti-inflammatory action by inhibiting leukocyte recruitment in vitro and in vivo.

血管生成，新血管的发育和生长，对于器官发育，伤口愈合和各种病理状况（例如肿瘤生长或增殖性视网膜病）至关重要。新生血管化取决于内皮细胞与细胞外基质以及生长因子功能的整合素介导的粘合剂接触。有新兴的证据表明炎性细胞，尤其是中性粒细胞调节与血管生成有关的内皮细胞功能。炎症细胞参与血管生成可能取决于生物学背景。已经描述了中性粒细胞的促血管生成和抗血管生成活性。中性粒细胞是生长因子和蛋白酶的来源。然而，中性粒细胞可以产生抗血管生成因子血管植物和α-防御素。 1）我们可以证明，α-防御素与纤连蛋白（FN）和α5Beta1-整合素形成三元络合物，并将FN-Alpha5Beta1-整合素相互作用转化为不促进内皮细胞粘附的一种。因此，α-防御素会干扰与体外和体内血管生成有关的内皮细胞功能。 2）抗血管生成因子血管毒素被鉴定为白细胞β2-整合素Mac-1的配体。因此，血管抑素被发现通过在体外和体内抑制白细胞募集来发挥抗炎作用。