Transcellular biosynthesis of cysteinyl leukotrienes in vivo during mouse peritoneal inflammation

摘要: Leukotrienes (LTs) are lipid mediators of inflammation formed by enzymatic oxidation arachidonic acid. One intriguing aspect LT production is transcellular biosynthesis: cells expressing 5-lipoxygenase (5LO) form LTA4 and transfer it to hydrolase (LTA4H) or LTC4 synthase (LTC4S) produce LTB4 LTC4. This process has been demonstrated in vivo for LTB4, but not cysteinyl LTs (cysLTs). We examined cysLT synthesis during zymosan-induced peritonitis, using bone marrow transplants with transgenic mice deficient key enzymes analyzing all eicosanoids liquid chromatography/tandem mass spectrometry. WT time-dependently produced cysLTs (LTC4, LTD4, LTE4). 5LO−/− were incapable producing LTs. restored this biosynthetic ability, did rescue irradiated mice, demonstrating that marrow-derived the ultimate source model. Total levels 5LO-derived products comparable LTA4H−/− reduced LTC4S−/− animals. No differences prostaglandin observed between these chimeric mice. Bone from injected into ability synthesize cysLTs, providing unequivocal evidence efficient biosynthesis cysLTs. These results highlight potential relevance exchange mediating biological activities inflammatory events vivo.