SMOOTH-MUSCLE CONTRACTION AND RELEASE OF HISTAMINE AND SLOW-REACTING SUBSTANCE OF ANAPHYLAXIS IN PULMONARY TISSUES-ISOLATED FROM GUINEA-PIGS PASSIVELY SENSITIZED WITH IGG1 OR IGE ANTIBODIES

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Abstract
Different Fc receptors mediate antigen-induced pulmonary smooth muscle contractile responses after passive sensitization of guinea pigs with IgG1 or IgE antibodies. The relationship between contraction and release of histamine and slow-reacting substance of anaphylaxis (leukotrienes) was examined in superfused trachea and parenchymal strips as well as mediator release from minced lung fragments after passive sensitization of guinea pigs with IgG1 or IgE antibodies. Guinea pigs were immunized to produce either IgG1 or IgG1 and IgE using oxazolone-guinea pig albumin or oxazolone-Ascaris plus cyclophosphamide, respectively. The contaminating IgG1 in the IgE-rich serum was removed by passage over a protein A-Sepharose column. Normal guinea pigs were passively sensitized i.p. or i.v. with injections of either IgG1 or IgE 1 or 2 days before in vitro studies. Superfused tissues were challenged with 10-1 mg/ml antigen (oxazolone-human serum albumin conjugate), and contractions and histamine and leukotriene release were monitored at discrete time intervals thereafter. At equivalent levels of contraction, substantially more histamine and leukotrienes were released from tissue taken from IgG1-sensitized animals. The amounts of histamine release from lung parenchymal strips and trachea in the IgE-sensitized state were .apprx. 5 and 38%, respectively, of those released from corresponding tissues in the IgG1-sensitized state. The leukotriene release from tissues isolated from IgE-sensitized animals was < 4% of the released from tissues in the IgG1-sensitized state. Similar differences in mediator release were seen in comparable studies on minced lung fragments. In all cases, the ratio of leukotriene bioactivity to histamine was larger in parenchyma than in trachea. In a study comparing active vs. passive sensitization, contraction and mediator release were not substantially different. A more rapid rise to peak contraction and histamine release were seen in the actively sensitized state. Quantitative differences in histamine and leukotriene release mediated by IgG1 and IgE antibodies in pulmonary tissues of the guinea pig are demonstrated. Qualitative differences exist in events leading to antigen-induced airway smooth muscle contraction mediated by the 2 antibodies.