Elsbach P, Weiss J, Doerfler M, Shu C, Kohn F, Ammons W S, Kung A H, Meszaros K K, Parent J B
Department of Medicine, New York University Medical Center, NY 10016.
Prog Clin Biol Res. 1994;388:41-51.
The Bactericidal/Permeability Increasing protein (BPI) is a major constituent of the azurophilic granules of human and rabbit polymorphonuclear leukocytes (PMN). The cDNA of the highly conserved protein has been isolated from man, rabbit and cow. The ca. 50 kDa BPI and a ca. 25 kDa bioactive N-terminal fragment are cytotoxic only for Gram-negative bacteria (GNB). This target-cell specificity reflects the strong attraction of the highly cationic protein for the negatively charged lipopolysaccharides (LPS) in the bacterial envelope. Native and recombinant (r) holo-BPI and the N-terminal fragment (rBPI-23) bind with high affinity (apparent Kd 1-10 nM) to all forms of isolated LPS so far examined, and inhibit the numerous biological effects of LPS in vitro (including in whole blood ex vivo) as well as in animals. Under the same conditions the antibacterial activities of holo-BPI and rBPI-23 against GNB with rough chemotype LPS are the same, but against serum-resistant and smooth chemotype GNB rBPI-23 is up to 30-fold more potent than holo-BPI. Holo-BPI and rBPI-23 protect mice, rats and rabbits against lethal cytotoxic effects of LPS and in some cases against lethal inoculations with live GNB.
杀菌/通透性增加蛋白（BPI）是人和兔多形核白细胞（PMN）嗜天青颗粒的主要成分。已从人、兔和牛中分离出这种高度保守蛋白的cDNA。约50 kDa的BPI和一个约25 kDa的生物活性N端片段仅对革兰氏阴性菌（GNB）具有细胞毒性。这种靶细胞特异性反映了这种高度阳离子化蛋白对细菌包膜中带负电荷的脂多糖（LPS）的强烈吸引力。天然和重组（r）全BPI以及N端片段（rBPI-23）与迄今为止检测的所有形式的分离LPS具有高亲和力（表观Kd为1-10 nM），并在体外（包括离体全血）以及在动物体内抑制LPS的多种生物学效应。在相同条件下，全BPI和rBPI-23对具有粗糙化学型LPS的GNB的抗菌活性相同，但对血清抗性和平滑化学型GNB，rBPI-23的效力比全BPI高30倍。全BPI和rBPI-23可保护小鼠、大鼠和兔免受LPS的致死性细胞毒性作用，在某些情况下还可免受活GNB的致死性接种。
