Moyle M, Foster D L, McGrath D E, Brown S M, Laroche Y, De Meutter J, Stanssens P, Bogowitz C A, Fried V A, Ely J A
Corvas International Inc., San Diego, California 92121.
J Biol Chem. 1994 Apr 1;269(13):10008-15.
The chronic survival of many endoparasites is dependent on the ability of these organisms to escape the host immune response. Identification of the molecular mechanisms by which these organisms evade this response may yield novel approaches in the development of anti-inflammatory agents. We describe here the discovery and characterization of a novel 41-kilodalton glycoprotein from the canine hookwork (Ancylostoma caninum) that potently inhibits CD11/CD18-dependent neutrophil function in vitro. Neutrophil inhibitory factor (NIF) blocks the adhesion of activated human neutrophils to vascular endothelial cells as well as the release of H2O2 from activated neutrophils, over a similar concentration range (IC50 10-20 nM). Studies aimed at determining the nature of the NIF binding site on neutrophils revealed selective, high affinity binding of this protein to the integrin CD11b/CD18. A cDNA encoding NIF was isolated from a canine hookworm cDNA library. NIF comprises a mature polypeptide of 257 amino acids, preceded by a 17-amino acid leader. The mature protein has 10 cysteines and has seven potential N-linked glycosylation sites. NIF has no significant sequence homologies to any previously reported protein. As such, NIF represents a prototype of a novel class of leukocyte function inhibitors.
许多体内寄生虫的长期存活取决于这些生物体逃避宿主免疫反应的能力。确定这些生物体逃避这种反应的分子机制可能会为抗炎药物的开发带来新方法。我们在此描述了一种来自犬钩虫（犬钩口线虫）的新型41千道尔顿糖蛋白的发现和特性，该糖蛋白在体外能有效抑制CD11/CD18依赖性中性粒细胞功能。中性粒细胞抑制因子（NIF）在相似的浓度范围内（IC50为10 - 20 nM）可阻断活化的人中性粒细胞与血管内皮细胞的黏附以及活化中性粒细胞释放H2O2。旨在确定NIF在中性粒细胞上结合位点性质的研究表明，该蛋白与整合素CD11b/CD18具有选择性的高亲和力结合。从犬钩虫cDNA文库中分离出了编码NIF的cDNA。NIF由257个氨基酸的成熟多肽组成，前面有一个17个氨基酸的前导序列。成熟蛋白有10个半胱氨酸，有7个潜在的N - 糖基化位点。NIF与任何先前报道的蛋白质均无明显的序列同源性。因此，NIF代表了一类新型白细胞功能抑制剂的原型。
