title: Complement-induced expression of cryptic receptors on the neutrophil surface: a mechanism for regulation of acute inflammation in trauma.
abstract: We explored the hypothesis that identified changes in neutrophil function in patients with acute injury result from in vivo exposure to C5a. To evaluate this hypothesis, we performed a battery of tests on 26 trauma patients (14 with blunt injury, 12 with penetrating injury). Measured were plasma levels of the complement activation products C3a and C5a; neutrophil chemotaxis to C5a and N-formyl-methionyl-leucyl-phenylalanine (FMLP); neutrophil receptors for FMLP and C3b; and superoxide response to FMLP and serum-opsonized zymosan. Patient responses measured within 48 hours of admission were divided into two groups based on neutrophil migratory response to C5a. Patients unresponsive to C5a (but responsive to FMLP) showed elevated plasma C3a levels (248 +/- 6 ng/ml) compared with patients with normal C5a migratory response (104 +/- 8 ng/ml). FMLP receptor number was markedly increased in the chemotactically deactivated group (group I: 155,680 +/- 100; group II: 51,200 +/- 200) and receptor affinity was diminished. Binding activity of C3b increased in the C5a-unresponsive cells to 126% that of controls versus 94% for normally responsive patient cells. Superoxide production was found to be significantly increased in patient cells with increased receptor numbers. These results support the concept that a subgroup of trauma patients manifest plasma and neutrophil changes compatible with complement activation. The neutrophil changes identified demonstrate a state of cellular activation. The clinical significance of these results may reside in a risk of pulmonary microvascular injury if activated cells are marginated and then subsequently stimulated.
mesh_terms: D002634:Chemotaxis, Leukocyte; D003167:Complement Activation; D003179:Complement C3b / Q000378:metabolism; D003182:Complement C5 / Q000378:metabolism; D015936:Complement C5a; D003165:Complement System Proteins / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000276:immunology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D013481:Superoxides / Q000378:metabolism; D014947:Wounds and Injuries / Q000150:complications / Q000276:immunology*
chemical_list: D003182:Complement C5; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; D044042:Receptors, Formyl Peptide; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003179:Complement C3b; D015936:Complement C5a; D003165:Complement System Proteins