HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Powell, W. S. Articles by Gravelle, F. Search for Related Content PubMed PubMed Citation Articles by Powell, W. S. Articles by Gravelle, F. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 265, Issue 16, 9131-9139, 06, 1990

Metabolism of arachidonic acid by peripheral and elicited rat polymorphonuclear leukocytes. Formation of 18- and 19-oxygenated dihydro metabolites of leukotriene B4

WS Powell and F Gravelle
Endocrine Laboratory, Royal Victoria Hospital, Montreal, Quebec, Canada.

Previous studies have shown that leukotriene B4 is metabolized by polymorphonuclear leukocytes (PMNL) by a 20-hydroxylase, a 19- hydroxylase, and a reductase. We have now identified for the first time LTB4 metabolites formed by a combination of the reductase and omega- oxidation pathways. We have also discovered that rat PMNL metabolize LTB4 by a novel pathway to 18-hydroxy products. Dihydro metabolites of LTB4 have formerly been reported only after incubation of exogenous LTB4 with PMNL, but we have now shown that they are formed to the same extent from endogenous arachidonic acid after stimulation of PMNL with the ionophore, A23187. The following metabolites have been identified after incubation of either LTB4 or arachidonic acid with rat PMNL: 10,11-dihydro-LTB4, 10,11-dihydro-12-epi-LTB4, 10,11-dihydro-12-oxo- LTB4, 19-hydroxy-LTB4, 19-hydroxy-10,11-dihydro-LTB4, 19-oxo-10,11- dihydro-LTB4, 18-hydroxy-LTB4, 18-hydroxy-10,11-dihydro-LTB4, and 18- hydroxy-10,11-dihydro-12-oxo-LTB4. Negligible amounts of 20- hydroxylated products were formed. Incubation of PMNL with 10,11- dihydro-LTB4 resulted in the formation of all of the above dihydro metabolites. However, none of the omega-oxidized metabolites of LTB4 was further metabolized to a significant extent when incubated with PMNL, possibly at least partially because they were not substrates for a specific LTB4 uptake mechanism. We found that the biosynthesis and metabolism of LTB4 is considerably enhanced in PMNL from an inflammatory site (carrageenan-induced pleurisy) compared with peripheral PMNL. When arachidonic acid was the substrate, the greatest increase was observed for products formed by the reductase pathway, which were about eight times higher in pleural PMNL. The rates of formation of both LTA hydrolase and omega-hydroxylase products were about three times higher, whereas the total amounts of 5-lipoxygenase products were about twice as high in pleural PMNL. The amounts of products formed by the above enzymatic pathways reached maximal levels about 4-6 h after injection of carrageenan and then declined.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Cossette, P. Patel, J. R. Anumolu, S. Sivendran, G. J. Lee, S. Gravel, F. D. Graham, A. Lesimple, O. A. Mamer, J. Rokach, et al. Human Neutrophils Convert the Sebum-derived Polyunsaturated Fatty Acid Sebaleic Acid to a Potent Granulocyte Chemoattractant J. Biol. Chem., April 25, 2008; 283(17): 11234 - 11243. [Abstract] [Full Text] [PDF]

				P. Christmas, K. Tolentino, V. Primo, K. Z. Berry, R. C. Murphy, M. Chen, D. M. Lee, and R. J. Soberman Cytochrome P-450 4F18 Is the Leukotriene B4 {omega}-1/{omega}-2 Hydroxylase in Mouse Polymorphonuclear Leukocytes: IDENTIFICATION AS THE FUNCTIONAL ORTHOLOGUE OF HUMAN POLYMORPHONUCLEAR LEUKOCYTE CYP4F3A IN THE DOWN-REGULATION OF RESPONSES TO LTB4 J. Biol. Chem., March 17, 2006; 281(11): 7189 - 7196. [Abstract] [Full Text] [PDF]

				C. Brink, S.-E. Dahlen, J. Drazen, J. F. Evans, D. W. P. Hay, G. E. Rovati, C. N. Serhan, T. Shimizu, and T. Yokomizo International Union of Pharmacology XLIV. Nomenclature for the Oxoeicosanoid Receptor Pharmacol. Rev., March 1, 2004; 56(1): 149 - 157. [Abstract] [Full Text] [PDF]

				K. A. Z. Berry, P. Borgeat, J. Gosselin, L. Flamand, and R. C. Murphy Urinary Metabolites of Leukotriene B4 in the Human Subject J. Biol. Chem., June 27, 2003; 278(27): 24449 - 24460. [Abstract] [Full Text] [PDF]

				J. M. Hevko, R. C. Bowers, and R. C. Murphy Synthesis of 5-Oxo-6,8,11,14-eicosatetraenoic Acid and Identification of Novel omega -Oxidized Metabolites in the Mouse Macrophage J. Pharmacol. Exp. Ther., April 13, 2001; 296(2): 293 - 305. [Abstract] [Full Text]

				T. G. Brock, R. W. McNish, M. B. Bailie, and M. Peters-Golden Rapid Import of Cytosolic 5-Lipoxygenase into the Nucleus of Neutrophils after in Vivo Recruitment and in Vitro Adherence J. Biol. Chem., March 28, 1997; 272(13): 8276 - 8280. [Abstract] [Full Text] [PDF]