Neutrophil dysfunction in sepsis. II. Evidence for the role of complement activation products in cellular deactivation.
Neutrophil dysfunction in sepsis. II. Evidence for the role of complement activation products in cellular deactivation.
复制标题
DOI：
--
复制
发表时间：
1981-08
期刊：
影响因子：
3.8
通讯作者：
J. Solomkin;Jenkins Mk;R. Nelson;D. Chenoweth;R. L. Simmons
中科院分区：
文献类型：
--
作者：
J. Solomkin;Jenkins Mk;R. Nelson;D. Chenoweth;R. L. Simmons
在烧伤、创伤和感染的患者中发现了趋化和杀菌活性的异常。这种异常可能导致菌血症或医院感染。这些异常的机制尚不清楚。我们研究了补体成分C5a对47例腹内感染和中性粒细胞功能紊乱患者趋化作用的影响。血浆C5a水平升高(102.1±8.3vs52.6士/-3.4ngml，P<0.01)。C5a与趋化性呈线性关系(r=0.56，P<0.01)。对患者中性粒细胞的检查显示，变化与非特异性失活一致。对N-甲硫基亮氨酰苯丙氨酸(FMLP)和活化血清(C5a)的趋化作用平行丧失(r=0.74，P<0.001)，对细胞内β-葡萄糖苷酸酶的趋化作用(r=0.82，P<0.001)，对C5a和FMLP的趋化作用(r=0.56，P<0.001)。受体分析显示C5a结合特异性丢失，但FMLP结合完整。趋化功能低下的患者将正常中性粒细胞暴露于血浆中，可导致类似的C5a受体丧失、FMLP和激活血清诱导的趋化作用在高血浆浓度时丧失，以及在低浓度时选择性丧失激活血清反应。这些数据支持这样一个概念，即在体内暴露于高水平的化学诱导剂(如C5a)后，中性粒细胞的非特异性趋化失活是导致腹部感染期间中性粒细胞功能障碍的主要因素。
Abnormalities in chemotactic and bactericidal activity have been identified in patients suffering from burn injury, trauma, and infection. Such abnormalities may lead to bacteremia or nosocomial infection. The mechanism for these abnormalities is unclear. We studied the role of chemotactic deactivation by complement component C5a in 47 patients with intra-abdominal infection and with disordered neutrophil function. Plasma C5a levels in such patients were elevated (102.1 +/- 8.3 versus 52.6 +/- 3.4 ng/ml for control subjects, P less than 0.01). There was a linear relationship between C5a and chemotaxis (r = 0.56, P less than 0.01). Examination of patients' neutrophils showed changes consistent with nonspecific deactivation. There were parallel losses of chemotaxis to N-formyl methionyl-leucyl-phenylalanine (FMLP) and activated serum (C5a) (r = 0.74, P less than 0.001), chemotaxis and intracellular beta-glucuronidase (r = 0.82, P less than 0.001), and C5a and FMLP chemotaxis and (r = 0.56, P less than 0.01). Receptor assays revealed specific loss of C5a binding but intact FMLP binding. Exposure of normal neutrophils to plasma from patients with depressed chemotaxis caused similar loss of C5a receptors and loss of FMLP and activated serum-induced chemotaxis at high plasma concentrations and selective loss of activated serum response at lower concentrations. These data support the concept that a major factor leading to neutrophil dysfunction during intra-abdominal infection is nonspecific chemotactic deactivation of neutrophils after in vivo exposure to high levels of chemoattractants such as C5a.