Enhancement of antigen-induced bronchoconstriction after intravascular complement activation with cobra venom factor: Reversal by granulocyte depletion

Our previous studies have demonstrated that activation of the C system with cobra venom factor (CVF) in a passively sensitized guinea pig results in an enhanced bronchoconstrictor response to Ag but not to other constrictor agents. Thus, our immediate goal was to determine the mechanism of the CVF-induced enhancement of the Ag-induced bronchoconstriction. Isolated airways from sensitized guinea pigs that had been treated with CVF responded normally to Ag. Because such a system lacks the normal circulating cell populations, we hypothesized that the CVF-induced enhancement of the Ag-induced bronchoconstriction was dependent on the presence of circulating white blood cells or platelets. Guinea pigs were depleted of circulating granulocytes, platelets, or both using specific antisera and the effect on the CVF-induced enhancement of the Ag-induced bronchoconstriction was determined. We found that CVF treatment did not result in an enhanced Ag-induced bronchoconstriction in guinea pigs depleted of either granulocytes or both granulocytes and platelets. However, the enhanced response was still apparent in guinea pigs depleted of just platelets. We investigated the effects of CVF itself and found that CVF treatment did not alter the number, or percentages, of different cell populations in the bronchoalveolar lavage, did not alter the protein or albumin content of the lavage fluid or the wet:dry ratio of the lung. In addition, CVF did not cause an increase in airway microvascular permeability as assessed by leakage of Evans blue. However, CVF did substantially increase granulocytes sequestered in the lung as measured by increased myeloperoxidase content. Thus, C activation by CVF results in an increase in neutrophils in the lung and an enhanced Ag-induced bronchoconstriction dependent on the presence of circulating granulocytes. These studies suggest that C activation and/or retention of granulocytes in the lung may be important in determining the severity of an Ag-induced bron-choconstriction.