Anaphylaxis in chopped guinea pig lung. III. Effect of carbon monoxide, cyanide, salicylaldoxime, and ionic strength.

Abstract

The anaphylactic release of histamine from perfused, chopped guinea pig lung is very sensitive to changes in the NaCl concentration of the containing medium, and it is ionic strength rather than particle concentration which is critical. Consequently, in studies with inhibitors care must be taken to avoid inadvertently increasing ionic strength and thereby misinterpreting the cause of the inhibition. Since immune hemolysis exhibits a similar sensitivity to changes in the NaCl concentration of the suspending medium, salicylaldoxime and phlorizin, which prevent the participation of the third component of complement in immune hemolysis, were investigated for their effect on the anaphylactic reaction. Salicylaldoxime is a potent inhibitor of in vitro anaphylaxis in guinea pig lung, but phlorizin is only a weak inhibitor. Potassium cyanide, 1 mM, inhibits the anaphylactic release of histamine most effectively if the duration of contact between the tissue and the cyanide prior to antigen addition is minimal; preincubation of the tissue with cyanide prior to antigen addition results in progressive diminution of inhibition even when there is only minimal loss of cyanide from the containing medium. The anaphylactic release of histamine from perfused whole lungs or suspensions of blood-free chopped lung is not prevented by the cytochrome oxidase inhibitor, carbon monoxide. In addition, 2-heptyl 4 hydroxyquinoline N oxide and malonic acid, which inhibit aerobic metabolism at different sites, do not prevent the reaction. These studies and those with cyanide indicate that the anaphylactic release of histamine in guinea pig lung is not dependent on cytochrome-mediated aerobic metabolism.