Phagocytosis Stimulates the Release of a Slow Reacting Substance in Cultured Macrophages

Abstract

1 A slow-reacting substance (SRS) was released from non-elicited mouse peritoneal macrophages during phagocytosis of zymosan particles, whereas no detectable SRS was produced by resting cells. 2 The macrophage SRS induced a delayed and slow contraction of the guinea-pig ileum but not of the chick rectum.3 The myotonic activity was antagonized by low concentrations of FPL 55712 (sodium 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)2-hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2 carboxylate) but was not affected by mepyramine or hyoscine, and was not associated with tachyphylaxis. 4 SRS release was increased by indomethacin and was abolished by the lipoxygenase and cyclooxygenase inhibitor, BW755C (3-amino-l-[m-(trifluoromethyl)phenyl]-2-pyrazoline). 5 Addition of exogenous arachidonic acid or cysteine enhanced SRS production.

The release of prostaglandin and slow reacting substance from mouse macrophages

“…This has been noted by other workers [3,5] and is also characteristic of the response to synthetic leukotriene C 4 [6]. Contractile responses to both human lung SRS-A and phagocytically derived macrophage SRS were antagonized by the SRS-A antagonist FPL 55712 which gave pA 2 values of 7.6 and 7.5 respectively indicating that the two substances were probably acting at the same receptor: The cyclooxygenase/lipoxygenase inhibitor BW755C inhibited the production of both PGE and SRS by macrophages but was more effective in inhibiting the production ofPGE (ICsoPGE 5 • 10 6M, ICsoSRS 5 • 10 -5 M).…”