IDENTIFICATION OF HAPTOGLOBIN AS AN ANGIOGENIC FACTOR IN SERA FROM PATIENTS WITH SYSTEMIC VASCULITIS
IDENTIFICATION OF HAPTOGLOBIN AS AN ANGIOGENIC FACTOR IN SERA FROM PATIENTS WITH SYSTEMIC VASCULITIS
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DOI：
10.1172/jci116319
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发表时间：
1993-03-01
影响因子：
15.9
通讯作者：
KLEINMAN, HK
中科院分区：
文献类型：
--
作者：
CID, MC;GRANT, DS;KLEINMAN, HK
血管生成是慢性炎症性疾病的重要过程。我们观察到，从系统性血管炎患者的血清刺激血管生成的体外模型，使用人脐静脉内皮细胞培养的基底膜（基质胶）基板。在40%硫酸铵沉淀后，血管生成活性保留在低分子量部分中，并且可以被热灭活。表现出最大血管生成活性的血清FPLC组分的SDS-聚丙烯酰胺凝胶电泳（SDS-page）证明在患者血清中有两种主要的45和16-20 kD的物质。这些条带在从对照受试者获得的血清中明显得多。45 kD蛋白的氨基末端测序证明它是触珠蛋白。纯化的触珠蛋白以剂量依赖性方式刺激血管生成。血管炎患者血清的血管生成活性被抗触珠蛋白抗体部分抑制。此外，血管炎患者的血清结合珠蛋白水平与疾病和血管生成活性相关。结合珠蛋白血管生成活性在两个体内模型中使用植入的椎间盘和皮下注射基底膜得到证实。刺激血管生成是触珠蛋白的一种新的生物学功能。在慢性炎症条件下发现的结合珠蛋白水平的增加可能在组织修复中起重要作用。在系统性血管炎中，触珠蛋白也可能通过促进侧支血管的发育来补偿缺血。
Angiogenesis is an important process in chronic inflammatory diseases. We observed that sera from patients with systemic vasculitis stimulated angiogenesis in an in vitro model using human umbilical vein endothelial cells cultured on a basement membrane (Matrigel) substrate. After 40% ammonium sulfate precipitation, angiogenic activity remained in the low molecular weight fraction and could be inactivated by heat. SDS-page of serum FPLC fractions exhibiting maximal angiogenic activity demonstrated two prominent species of 45 and 16-20 kD in patients' sera. These bands were much less apparent in sera obtained from control subjects. Amino-terminal sequencing of the 45-kD protein demonstrated that it was haptoglobin. Purified haptoglobin stimulated angiogenesis in a dose-dependent manner. The angiogenic activity of vasculitis patients' sera was partially inhibited by an antihaptoglobin antibody. Furthermore, serum haptoglobin levels in vasculitis patients correlated both with disease and angiogenic activity. Haptoglobin angiogenic activity was confirmed in two in vivo models using an implanted disc and a subcutaneous injection of basement membrane. Stimulation of angiogenesis is a newly recognized biological function of haptoglobin. The increased levels of haptoglobin found in chronic inflammatory conditions may play an important role in tissue repair. In systemic vasculitis, haptoglobin might also compensate for ischemia by promoting development of collateral vessels.