Carrette O, Mizon C, Balduyck M, Jourdain M, Fourrier F, Mizon J
Laboratoire de Biochimie (DRED EA1052), Faculté de Pharmacie, Lille, France.
Biochimie. 1997 Dec;79(12):749-55. doi: 10.1016/s0300-9084(97)86933-7.
The unrestricted activity of leukocyte proteinases is thought to contribute to the degradation of plasma proteins and thus amplify the coagulation disorders occurring in septic shock. Inter-alpha-inhibitor (I alpha I) is a plasma protein particularly susceptible to their action. Therefore we investigated its behavior in a porcine model of endotoxin shock which reproduces the coagulation changes observed in human sepsis. We did not detect any qualitative or quantitative modification of porcine I alpha I in plasmas collected from pigs after endotoxin infusion. To explain these data, I alpha I was incubated with polymorphonuclear neutrophils (PMN) stimulated by FMLP in the presence of cytochalasin B. We found that, unlike human PMN, porcine cells were unable to proteolyze I alpha I. Moreover, in the incubation medium of pig PMN, triggered either by FMLP or PMA, no measurable elastase activity was evidenced. Therefore, we urge to better take into account species differences in functional responses of PMN, to explain the experimental results obtained in animal models of septic shock.
白细胞蛋白酶的无限制活性被认为会导致血浆蛋白降解,从而加剧脓毒性休克中出现的凝血紊乱。α-抑制因子(IαI)是一种特别容易受其作用影响的血浆蛋白。因此,我们在一种内毒素休克猪模型中研究了它的行为,该模型再现了人类脓毒症中观察到的凝血变化。在内毒素注入后从猪身上采集的血浆中,我们未检测到猪IαI有任何定性或定量的改变。为了解释这些数据,我们将IαI与在细胞松弛素B存在下由N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸(FMLP)刺激的多形核中性粒细胞(PMN)一起孵育。我们发现,与人类PMN不同,猪细胞无法对IαI进行蛋白水解。此外,在由FMLP或佛波酯(PMA)触发的猪PMN孵育培养基中,未检测到可测量的弹性蛋白酶活性。因此,我们敦促在解释脓毒性休克动物模型中获得的实验结果时,更好地考虑PMN功能反应中的物种差异。