Neutrophil dysfunction in sepsis. II. Evidence for the role of complement activation products in cellular deactivation.
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.
D000293:Adolescent; D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000097:blood* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003167:Complement Activation; D003182:Complement C5 / Q000032:analysis / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009239:N-Formylmethionine / Q000031:analogs & derivatives / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology
D003182:Complement C5; D009842:Oligopeptides; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine