Rat alpha 2 macroglobulin is a selective inhibitor of antigen-induced leucotrienes in rat isolated lungs

Exogenously administered, purified rat alpha 2 macroglobulin (alpha 2M, recognized as an acute phase reactant with anti-inflammatory properties) greatly inhibits the increase of the pulmonary resistance during the antigen-induced bronchoconstriction in rats in vivo, whereas a BaSO4 pretreatment (a method to induce a broad spectrum of serum acute phase reactants, including alpha 2M) covers a broader bronchoprotection: suppression of the decrease of the dynamic lung compliance as well. To explain these differences we studied the influence of both alpha 2M and BaSO4 on the antigen-induced bronchoconstriction in rat isolated lungs in relation to the mediator release in lung-effluents. We report here that in this model alpha 2M only inhibits the antigen-induced SRS-A release, whereas the concomitant release of histamine and 5-HT was unaffected. As distinct from alpha 2M the BaSO4 pretreatment suppressed both the antigen-induced bronchoconstriction and the histamine, 5-HT and SRS-A release to a high extent. These data suggest that alpha 2M can be considered as a selective inhibitor of leucotrienes, which offers an explanation for several anti-inflammatory properties of alpha 2M, including protection against the antigen-induced increase of the pulmonary resistance in vivo.