Modulation of the immunological response of guinea pig mast cells by carbon monoxide

Challenge of guinea pig mast cells with antigen under aerobic conditions in duced the expected release of histamine and led to a significant increase i n intracellular calcium ([Ca2+](i)) and cyclic adenosine monophosphate (cAM P) levels. Prior exposure to CO decreased the immunological histamine relea se. This effect was accompanied by a decrease in the levels of [Ca2+](i) an d by an increase in the cyclic guanosine monophosphate (cGMP) levels. The e xposure of mast cells to nitrogen (N-2) did not modify the release of hista mine. The GO-mediated inhibition of the immunological release of histamine was reversed by the soluble guanylate cyclase inhibitor (1H-[1,2,4]oxadiazo lo[4,3-a]quinoxalin-1-one, ODQ) and by oxyhaemoglobin (HbO(2)). Incubation of mast cells for 4 h with hemin, a heme oxygenase(HO) inducer, resulted in an increase in HO activity, measured as bilirubin production. Hemin abated the immunological release of histamine, in similar fashion to exogenous CO , and increased the cGMP levels. These effects were reversed by ODQ and HbO (2). It is proposed that CO from an exogenous or endogenous source stimulat es guanylyl cyclase and causes cGMP formation which then induces calcium to be sequestrated so that the [Ca2+](i) concentration falls and histamine re lease is inhibited. (C) 1999 Elsevier Science B.V. All rights reserved.