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 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wightman, P. D. Articles by Dallob, A. Search for Related Content PubMed PubMed Citation Articles by Wightman, P. D. Articles by Dallob, A. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 265, Issue 16, 9176-9180, 06, 1990

Regulation of phosphatidylinositol breakdown and leukotriene synthesis by endogenous prostaglandins in resident mouse peritoneal macrophages

PD Wightman and A Dallob
Department of Biochemistry and Molecular Biology, Merck, Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065.

Mouse peritoneal macrophages synthesize large amounts of prostaglandins and leukotrienes in response to certain inflammatory stimuli. Lipopolysaccharide and phorbol esters stimulate prostaglandin formation but not leukotriene synthesis. Zymosan and the calcium ionophore, A23187, stimulate the formation of both prostaglandins and leukotrienes, as well as the phospholipase C-catalyzed breakdown of phosphoinositides. We have examined the interrelationships among phosphoinositide breakdown and prostaglandin and leukotriene synthesis in resident mouse peritoneal macrophages. We demonstrate that macrophages synthesize basally prostaglandin (PG)E2 and PGI2 and that these products begin to accumulate from the time of initial plating of the macrophages. The presence of these prostaglandins imparts a downward modulation of zymosan-stimulated phosphoinositide breakdown and, as a result, a downward modulation on leukotriene formation. Inhibition of the basal release of prostaglandin by indomethacin resulted in enhanced zymosan-stimulated phosphoinositide breakdown and an exactly corresponding enhancement of leukotriene release. This enhancement, resulting from the inclusion of indomethacin at the time of plating, was reversed by also including PGE2, PGI2, or dibutyryl cAMP. Dibutyryl cAMP, when added in the presence of zymosan and in the absence of indomethacin treatment, inhibited phosphoinositide breakdown and leukotriene synthesis in a parallel fashion, with no effect on prostaglandin release. These data demonstrate that phospholipase C activation is regulated in part by prostaglandin tone and that leukotriene synthesis, unlike prostaglandin synthesis, is dependent on phosphoinositide breakdown.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P.B. Myrdal, K. Karlage, P.J. Kuehl, B.S. Angersbach, B.A. Merrill, and P.D. Wightman Effects of novel 5-lipoxygenase inhibitors on the incidence of pulmonary adenomas in the A/J murine model when administered via nose-only inhalation Carcinogenesis, May 1, 2007; 28(5): 957 - 961. [Abstract] [Full Text] [PDF]

				M. Luo, S. M. Jones, N. Flamand, D. M. Aronoff, M. Peters-Golden, and T. G. Brock Phosphorylation by Protein Kinase A Inhibits Nuclear Import of 5-Lipoxygenase J. Biol. Chem., December 9, 2005; 280(49): 40609 - 40616. [Abstract] [Full Text] [PDF]

				M. Luo, S. M. Jones, S. M. Phare, M. J. Coffey, M. Peters-Golden, and T. G. Brock Protein Kinase A Inhibits Leukotriene Synthesis by Phosphorylation of 5-Lipoxygenase on Serine 523 J. Biol. Chem., October 1, 2004; 279(40): 41512 - 41520. [Abstract] [Full Text] [PDF]