Release of slow-reacting substance of anaphylaxis from dispersed pig lung cells: effect of cyclo-oxygenase and lipoxygenase inhibitors |
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Authors: | N A M Paterson MB FRCP J F Burka PhD I D Craig MB |
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Institution: | N. A. M. Paterson M.B., F.R.C.P.(C), J. F. Burka Ph.D.,I. D. Craig M.B. |
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Abstract: | Study of the release of slow-reacting substance of anaphylaxis (SRS-A).from lung cells has been hampered by the lack of a 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 pglcell). 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/107 cells) when challenged with Ascaris antigen. Greater release of histamine (mean net release 52%) and of slow-reacting substance (SRS) (mean release 701 units/107 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 SRS-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 μM) and eicosatetraenoic acid (IC50 15 μM), 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. |
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Keywords: | Reprint requests to: Dr Nigel A M Paterson Victoria Hospital Corporation Westminster Campus 777 Baseline Road East London Ontario Canada N6A 4S2 |
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