Enhancement of antigen-induced bronchoconstriction in the guinea pig after intravascular complement activation with cobra venom factor.
The purpose of the present studies was to begin to test the hypothesis that the complement system is important for antigen-induced bronchoconstriction in the guinea pig. The effect of the complement-depleting agent cobra venom factor (CVF) on antigen-induced bronchoconstriction in guinea pigs passively sensitized with IgG or IgE antibody to ovalbumin was determined. Intravenous injection of CVF significantly reduced total hemolytic complement activity (CH50), caused a transient decrease in dynamic lung compliance, an increase in pulmonary resistance, and a decrease in circulating white blood cells with a sustained decrease in platelets. Antigen-induced bronchoconstriction was not inhibited in either IgG- or IgE-sensitized guinea pigs depleted of complement. Thus, a role for the complement system as a contributing factor in antigen-induced bronchoconstriction was not supported. On the contrary, our studies revealed an enhanced antigen-induced bronchoconstriction in guinea pigs depleted of complement with CVF. Our studies were then directed towards characterizing the enhanced response to begin to determine the mechanism responsible. The enhanced antigen-induced bronchoconstriction occurred in both IgG- and IgE-sensitized guinea pigs and was most apparent at lower antigen doses. The enhanced response still occurred in animals treated for 5 min with a dose of CVF (10 U) which caused no demonstrable decrease in CH50, a 30% level of conversion of C3, and a normal response to C5a. These data suggested that the enhanced response was not related to the level of C5a responsiveness of the animal.(ABSTRACT TRUNCATED AT 250 WORDS)
Regal
J F
JF
Department of Pharmacology, University of Minnesota-Duluth School of Medicine.
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001986:Bronchial Spasm / Q000276:immunology*; D003167:Complement Activation; D004546:Elapid Venoms / Q000008:administration & dosage* / Q000494:pharmacology; D006168:Guinea Pigs; D007114:Immunization; D007275:Injections, Intravenous; D008170:Lung Compliance / Q000187:drug effects; D008297:Male
D000276:Adjuvants, Immunologic; D000941:Antigens; D004546:Elapid Venoms; C016310:cobra venom factor