Simultaneous initiation of degranulation and inhibition of leukotriene release by soman in human basophils.
Previous studies noted that the serine esterase inhibitor, soman, could induce histamine release from human basophils. To investigate the mechanisms by which soman causes histamine release (a preformed mediator), we also examined its ability to induce leukotriene release (a newly synthesized mediator) from basophils. We found that no leukotriene release followed activation with soman, while histamine release was usually greater than 70%. In addition, soman and diisopropyl-fluorophosphate were found actively to suppress low level spontaneous leukotriene release as well as ongoing leukotriene release induced by anti-IgE antibody. Soman (0.3 mM) was able to stop leukotriene release as rapidly as the calcium chelator, EDTA. In a series of control experiments, it was noted that soman did not influence the metabolism of LTC4 to LTD4 or LTE4 (for which little metabolism occurred), eliminating the possibility that reduced LTC4 release could have resulted from its enhanced metabolism. Therefore, using one compound (soman), basophils could be simultaneously activated to degranulate while having the pathway leading to leukotriene release actively suppressed. These results provide further evidence that histamine and leukotriene release are independent pathways resulting from the activation of basophils.
Meier
H L
HL
Research Institute of Chemical Defense, Aberdeen Proving Grounds, MD 21010, USA.
Warner
J
J
MacGlashan
D W
DW
D015549:Basophil Degranulation Test; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007531:Isoflurophate / Q000494:pharmacology; D017997:Leukotriene C4 / Q000378:metabolism*; D017998:Leukotriene D4 / Q000096:biosynthesis; D017999:Leukotriene E4 / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D012999:Soman / Q000494:pharmacology*
D006633:Histamine Antagonists; D007531:Isoflurophate; D017997:Leukotriene C4; D007073:Immunoglobulin E; D017998:Leukotriene D4; D017999:Leukotriene E4; D012999:Soman; D004492:Edetic Acid