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Research Article Free access | 10.1172/JCI109412

Specific Inhibition of the Polymorphonuclear Leukocyte Chemotactic Response to Hydroxy-Fatty Acid Metabolites of Arachidonic Acid by Methyl Ester Derivatives

Edward J. Goetzl, Frank H. Valone, Vernon N. Reinhold, and Robert R. Gorman

Howard Hughes Medical Institute Laboratory at Harvard Medical School, Departments of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Robert B. Brigham Hospital Division of the Affiliated Hospitals Center, Boston, Massachusetts 02115

Laboratory of Human Reproduction and Reproductive Biology, Harvard Medical School, Boston, Massachusetts 02115

The Upjohn Company, Kalamazoo, Michigan 49001

Find articles by Goetzl, E. in: PubMed | Google Scholar

Howard Hughes Medical Institute Laboratory at Harvard Medical School, Departments of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Robert B. Brigham Hospital Division of the Affiliated Hospitals Center, Boston, Massachusetts 02115

Laboratory of Human Reproduction and Reproductive Biology, Harvard Medical School, Boston, Massachusetts 02115

The Upjohn Company, Kalamazoo, Michigan 49001

Find articles by Valone, F. in: PubMed | Google Scholar

Howard Hughes Medical Institute Laboratory at Harvard Medical School, Departments of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Robert B. Brigham Hospital Division of the Affiliated Hospitals Center, Boston, Massachusetts 02115

Laboratory of Human Reproduction and Reproductive Biology, Harvard Medical School, Boston, Massachusetts 02115

The Upjohn Company, Kalamazoo, Michigan 49001

Find articles by Reinhold, V. in: PubMed | Google Scholar

Howard Hughes Medical Institute Laboratory at Harvard Medical School, Departments of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Robert B. Brigham Hospital Division of the Affiliated Hospitals Center, Boston, Massachusetts 02115

Laboratory of Human Reproduction and Reproductive Biology, Harvard Medical School, Boston, Massachusetts 02115

The Upjohn Company, Kalamazoo, Michigan 49001

Find articles by Gorman, R. in: PubMed | Google Scholar

Published June 1, 1979 - More info

Published in Volume 63, Issue 6 on June 1, 1979
J Clin Invest. 1979;63(6):1181–1186. https://doi.org/10.1172/JCI109412.
© 1979 The American Society for Clinical Investigation
Published June 1, 1979 - Version history
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Abstract

The human polymorphonuclear (PMN) leukocyte chemotactic activity of the hydroxy-fatty acid metabolites of arachidonic acid, 12-l-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 12-l-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), is eliminated by methylation. Both methyl esters are specific competitive inhibitors of the PMN leukotactic responses to the parent stimuli, and exert no effect on the responses to formyl-methionyl peptides or chemotactic fragments of the fifth component of complement. 50% inhibition of the in vitro chemotactic responses of PMN leukocytes to HETE and HHT was achieved by an equimolar concentration of the corresponding methyl esters, whereas reciprocal cross-inhibition was observed at molar ratios of HETE methyl ester to HHT and HHT methyl ester to HETE which reflected the three- to fivefold greater chemotactic potency of HETE relative to HHT. Methyl esters of structurally related, but nonchemotactic, fatty acids did not competitively inhibit the chemotaxis elicited by HETE or HHT. The intraperitoneal injection of HETE in guinea pigs evoked an eosinophil response at 30 min and a neutrophil response at 5 h, which were prevented by a one-to twofold molar ratio of HETE methyl ester. The competitive inhibition of the in vitro chemotactic activity and the in vivo leukotactic effect of the unsaturated hydroxy-fatty acids by homologous methyl ester derivatives suggests that the cellular component of natural inflammatory reactions may be susceptible to specific regulation by receptor-directed modulation of the activity of the predominant chemotactic principles.

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