Release of slow-reacting substance of anaphylaxis from dispersed pig lung cells: effect of cyclo-oxygenase and lipoxygenase inhibitors

Study of the release of slow-reacting substance of anaphylaxis (SRS-A) from lung cells has been hampered by the lack of suitable animal model. Using both immunologic and pharmacologic stimuli, we have obtained histamine and SRS-A release from dispersed pig lung cells containing 6% mast cells (with a histamine content of 1.9 pg/cell). Lung cells dispersed from actively sensitized (with intratracheal Ascaris antigen) but not unsensitized pigs released both histamine (mean net release 33%) and SRS-A (mean release, 47 units/10(7) cells) when challenged with Ascaris antigen. Greater release of histamine (mean net release 52%) and of slow-reacting substance (SRS) (mean release 701 units/10(7) cells) was induced by challenge with the calcium ionophore A23187. The pharmacologic and physicochemical characteristics of the SRS together with its profile of enzymatic inactivation resembled those described for SRA-A released from human lung. Both antigen-induced and A23187-induced SRS(-A) release were enhanced by indomethacin, a cyclo-oxygenase inhibitor, but inhibited by both phenidone (IC50 35 microM) and eicosatetraenoic acid (IC50 15 microM), inhibitors of both cyclo-oxygenase and lipoxygenase, confirming that generation of SRS(-A) by either stimulus required an intact lipoxygenase pathway of arachidonic acid metabolism.