Complement and neutrophil activation during cardiopulmonary bypass: a study in the complement-deficient dog.
Cardiopulmonary bypass (CPB) is known to cause complement and neutrophil activation, but the relative importance and interaction of these components in CPB-induced inflammation is unknown. In this study, a strain of dogs genetically deficient in the third component of complement (C3) was used to determine the contribution of C3 to neutrophil activation and pulmonary injury after CPB. Eleven dogs (5 C3-deficient and 6 controls) underwent 150 minutes of hypothermic CPB (28 degrees C) followed by 2 hours of observation. Before CPB, C3 levels were normal in controls and less than 1% of normal in C3-deficient dogs. In control dogs, functional activity of C3 decreased to 53.2% of baseline after 1 hour of CPB and there was immunohistochemical evidence of C3 deposition in lung after CPB; C3-deficient dogs had no C3 deposition in lung. Although similar degrees of neutropenia occurred during CPB in the two groups, expression of neutrophil adhesion molecule subunit CD18 was significantly lower in C3-deficient dogs than controls after 1 hour of CPB (45.9 +/- 3.7 versus 82.9 +/- 10.0 mean fluorescence units; p < 0.02). Postbypass lung tissue myeloperoxidase content was also less in C3-deficient dogs (43.8 +/- 4.6 versus 71.1 +/- 8.6 mumol x 10 mg-1 x min-1; p < 0.03). Cardiopulmonary bypass-associated lung injury (assessed by alveolar-arterial oxygen gradient, pulmonary vascular resistance, percent lung water, and light and electron microscopic appearance) was similar between groups. These results demonstrate that (1) C3 is deposited on pulmonary vascular endothelium during CPB and (2) C3 mediates increased expression of neutrophil CD18 and neutrophil sequestration in lung after CPB.(ABSTRACT TRUNCATED AT 250 WORDS)
Gillinov
A M
AM
Division of Cardiac Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Redmond
J M
JM
Winkelstein
J A
JA
Zehr
K J
KJ
Herskowitz
A
A
Baumgartner
W A
WA
Cameron
D E
DE
D000818:Animals; D015703:Antigens, CD / Q000302:isolation & purification; D018821:CD18 Antigens; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D003167:Complement Activation; D003176:Complement C3 / Q000172:deficiency / Q000276:immunology; D004285:Dogs; D015633:Extravascular Lung Water; D008213:Lymphocyte Activation; D009504:Neutrophils / Q000276:immunology*; D009195:Peroxidase / Q000097:blood; D011652:Pulmonary Circulation; D016028:Receptors, Leukocyte-Adhesion / Q000302:isolation & purification; D014655:Vascular Resistance
D015703:Antigens, CD; D018821:CD18 Antigens; D003176:Complement C3; D016028:Receptors, Leukocyte-Adhesion; D009195:Peroxidase