REGULATION OF THE SYNTHESIS AND RELEASE OF SLOW-REACTING SUBSTANCE OF ANAPHYLAXIS FROM SENSITIZED MONKEY LUNG

  • 1 January 1982
    • journal article
    • research article
    • Vol. 221  (2) , 295-302
Abstract
Immunological challenge of sensitized fragmented cynomolgus monkey lung with antihuman IgE induced the appearance of slow-reacting substance of anaphylaxis (SRS-A) in the tissue and evoked the release of SRS-A into the Tyrode''s supernatant. The elevation of tissue or residual SRS-A levels was maximal 2 min after anti-IgE challenge and remained at that plateau for at least 60 min. The released SRS-A, first detectable 3-5 min after challenge, achieved a plateau by 10 min. The released and residual SRS-A were similarly inactivated by soybean lipoxidase and were antagonized by FPL 55712 [7-[-4-acetyl-3-hydroxyl-2-propylphenoxy]-2-hydroxypropoxy]-4-oxo-8-propyl-4-m-1-benzopyran-2-carboxylic acid monosodium salt] on the guinea pig ileum. Isoproterenol, 5,8,11,14-eicosatraynoic acid and SK and F 64398 all inhibited the anti-IgE-induced elevation in residual SRS-A and blocked SRS-A release. Indomethacin stimulated the elevation of residual SRS-A and the amount released. Removal of the Tyrode''s supernatant containing 209 .+-. 73 U of released SRS-A/g of tissue 20 min after anti-IgE resulted in the release of an additional 239 .+-. 69 U/g; residual SRS-A levels remained at the plateau level. Incubation of the Tyrode''s supernatant from challenged, but not control, tissue with fresh lung tissue caused a 90 .+-. 7% inhibition of SRS-A release) from the fresh tissue. Leukotriene D4 [LTD] at 5-150 ng/ml (concentrations relevant to SRS-A release) showed a concentration-dependent inhibition of SRS-A release but no effect on histamine release. Leukotriene C4 at 5-50 ng/mg failed to significantly alter the amount of SRS-A release. At 150 ng/ml, significant inhibition was observed which may have been produced by metabolism to LTD. A potential role for LTD in regulating the amount of SRS-A release from monkey lung is demonstrated.