Characterization of the anaphylatoxin inactivator and chemotactic factor inactivator activities during cardiopulmonary bypass.
Complement activation productive of phlogistic products has been suggested as one of the major mechanisms of the pump lung syndrome associated with cardiopulmonary bypass (CPB) surgery. Recent studies have demonstrated the presence of circulating C3a antigens in the serum of patients undergoing CPB and have suggested that the vasoactive nature of C3a may contribute directly to the interstitial edema and vascular changes seen in pump lung syndrome. In an effort to unravel the underlying mechanisms of pump lung syndrome, we undertook investigations to determine whether CPB and associated complement activation would alter the serum levels of the major regulators of both C3a and C5a complement split products. These serum regulators designated chemotactic factor inactivator (CFI) and anaphylatoxin inactivator (AI) were measured in the serum of patients undergoing CPB. In these studies, we demonstrated that during CPB a rapid and dramatic drop in the anaphylatoxin inactivator activities occurred within the first 10 minutes of CPB. These lowered AI levels were maintained throughout the CPB but AI levels returned to normal within 24 hours postsurgery. CFI levels were generally maintained throughout the CPB surgery with only minimal depressions in CFI levels during or after CPB surgery. These studies clearly demonstrate that the major regulator system of the complement-derived vasopermeability factors (C3a and C5a) is dramatically depressed during cardiopulmonary bypass and may suggest that the mechanisms of interstitial edema associated with pump lung syndrome may at least, in part, be related to the loss of the serum regulator enzyme carboxypeptidase N, also designated AI.
D000706:Anaphylatoxins / Q000037:antagonists & inhibitors*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors*; D003176:Complement C3 / Q000378:metabolism; D015926:Complement C3a; D003182:Complement C5 / Q000378:metabolism; D015936:Complement C5a; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000098:blood supply; D001121:Lysine Carboxypeptidase / Q000378:metabolism; D010455:Peptides / Q000037:antagonists & inhibitors*; D011654:Pulmonary Edema / Q000209:etiology; D012120:Respiration Disorders / Q000209:etiology; D014652:Vascular Diseases / Q000209:etiology
D000706:Anaphylatoxins; D002630:Chemotactic Factors; D003176:Complement C3; D003182:Complement C5; D010455:Peptides; D015926:Complement C3a; D015936:Complement C5a; D001121:Lysine Carboxypeptidase