Enhancement of Antigen-Induced Bronchoconstriction in the Guinea Pig after Intravascular Complement Activation with Cobra Venom Factor

Abstract

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. In addition, CVF-treated animals were normally responsive to various purported mediators of antigen-induced bronchoconstriction: histamine, leukotriene C₄, platelet activating factor, the thromboxane-mimetic U-46,619, and prostaglandin F_2α. The response to prostaglandin D₂ was slightly enhanced. Thus, CVF treatment did not result in a generalized airway hyperreactivity. Since antigen-induced bronchoconstriction was not inhibited in animals depleted of complement, these studies suggest that an intact complement system is not necessary for this antigen-induced event. However, the enhanced antigen-induced bronchoconstriction seen after CVF treatment suggests that complement depletion and/or activation in vivo may be an important modulator or determinant of the severity of a subsequent antigen-induced bronchoconstriction.