Cardiac anaphylaxis. Complement activation as an amplification system.
Complement is activated, and C3a and C5a anaphylatoxins are generated during hypersensitivity reactions clinically associated with cardiopulmonary collapse. The administration of C3a or C5a to nonsensitized isolated guinea pig hearts mimics the events caused by antigen challenge of sensitized hearts (i.e., cardiac anaphylaxis) in the absence of complement. Thus, complement-derived anaphylatoxins may participate in immediate hypersensitivity reactions in which the heart is a target organ. To assess the contribution of complement activation and anaphylatoxin generation to cardiac dysfunction, we have elicited anaphylaxis in isolated guinea pig hearts in the presence of complement and found that the ensuing dysfunction is markedly enhanced. This amplification is most likely attributable to anaphylatoxin formation because 1) inactivation of C3 or selective C3 depletion, i.e., the loss of the component responsible for the formation of the anaphylatoxins C3a and C5a, prevents complement-induced exacerbation of cardiac anaphylaxis, whereas reconstitution with C3 and C5, or even only C3, restores it; in fact, the greater the C3 content at the time of antigen challenge, the more intense the anaphylactic crisis; and 2) the severity of cardiac anaphylaxis is markedly reduced by preexposure to C3a, and this reduction is directly related to the dose of C3a injected and to the amount of endogenous cardiac histamine depleted by C3a before antigen challenge. Complement-derived anaphylatoxins appear to promote the same mediator release that has been initiated by the antigen-antibody reaction; thus, complement activation functions as an amplification system in cardiac anaphylaxis.
del Balzo
U
U
Department of Pharmacology, Cornell University Medical College, New York, NY 10021.
Polley
M J
MJ
Levi
R
R
D000706:Anaphylatoxins; D000707:Anaphylaxis; D000818:Animals; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology; D015926:Complement C3a; D003182:Complement C5 / Q000276:immunology; D015936:Complement C5a; D003326:Coronary Circulation; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D006636:Histamine Release; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000276:immunology*
D000706:Anaphylatoxins; D003176:Complement C3; D003182:Complement C5; D015926:Complement C3a; D015936:Complement C5a