Leukotriene B4 omega-hydroxylase activity in polymorphonuclear leukocytes from patients with inflammatory bowel disease.
omega-oxidation is regarded as the major pathway for the catabolism of leukotriene B4 (LTB4). To determine how LTB4 omega-hydroxylase is modulated in inflammatory bowel disease, we investigated the kinetic characteristics of this enzyme in 10 patients with Crohn's disease (CD), nine with ulcerative colitis (UC) and eight healthy control subjects. After incubating polymorphonuclear leukocytes with various concentrations of 3H-labeled LTB4, omega-oxidation products were separated by high performance liquid chromatography (HPLC) and the radioactivity was measured by a liquid scintillation counter. The apparent Vmax values were significantly higher in both disease than in healthy control subjects, although the difference between CD and UC was insignificant. There was no difference in the apparent Km values. And the Vmax/Km ratios of patients with CD were significantly higher than that of healthy control subjects. It is suggested that LTB4 metabolism is activated in inflammatory bowel disease (IBD) and that the modulation of this enzyme activity has an important role in the pathogenesis of inflammatory bowel disease.
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
A
A
Ikehata
N
N
Hiwatashi
Y
Y
Kinouchi
K
K
Ito
H
H
Yamazaki
T
T
Toyota
D000293:Adolescent; D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000201:enzymology*; D003424:Crohn Disease / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000072470:Cytochrome P450 Family 4; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*
D007975:Leukotriene B4; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D000072470:Cytochrome P450 Family 4; C040780:leukotriene B4 20-hydroxylase