Transformation of leukotriene A4 to lipoxins by rat kidney mesangial cell.
Incubation of rat mesangial cells with leukotriene A4 in the presence of calcium ionophore A23187 led to a substrate dependent formation of lipoxin and its isomers. The major metabolite coeluted with authentic lipoxin A4 (LXA4) and lipoxin B4 (LXB4) in RP-HPLC system, and possessed a characteristic U.V. spectrum and C-value which were identical to authentic standards. GC/MS analysis on LXA4 further demonstrates that the mesangial cell derived LXA4 was identical to that reported by Serhan et al. (1) as LXA4 [5(S), 6,(R), 15(S)-trihydroxy7,9,13-trans-11-cis-eicosatetraenoic acid]. The formation of LXA4 was linear with substrate (LTA4) concentration. No similar products occurred in boiled controls. Incubation of mesangial cell with 15-HPETE failed to produce any lipoxin-like material. The absence of LX-like substance following incubation of 15-HPETE with mesangial cells suggested that 5-lipoxygenase activity is not expressed in mesangial cells under these conditions. The generation of LXA4 from LTA4 in mesangial cells suggested that there is an active 15- or 12- lipoxygenase activity in the kidney. The production of LX may play an important role in the regulation of renal function and the response to inflammatory stimuli.
Garrick
R
R
Department of Medicine, New York Medical College, Valhalla 10595.
Shen
S Y
SY
Ogunc
S
S
Wong
P Y
PY
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D017572:Leukotriene A4; D015289:Leukotrienes / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D044045:Lipoxins; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D017572:Leukotriene A4; D015289:Leukotrienes; D008054:Lipid Peroxides; D044045:Lipoxins; C040527:lipoxin A4; D016718:Arachidonic Acid; D000001:Calcimycin; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C042651:lipoxin B4; D001094:Arachidonate 5-Lipoxygenase