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PMID: 2989173 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Characterization of effect of N-formyl-methionyl-leucyl-phenylalanine on leukotriene synthesis in human polymorphonuclear leukocytes.

Inflammation ·Vol. 9 ·No. 2 ·1985-06-00 ·Pages 127-38

Salari H, Braquet P, Naccache P, Borgeat P

Abstract

Human polymorphonuclear leukocytes (PMNLs) were exposed to N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe) in the presence or absence of exogenous arachidonic acid. Analysis of incubation mixtures by high-performance liquid chromatography showed that f-Met-Leu-Phe stimulated the synthesis of 5-hydroxy-eicosatetraenoic acid (HETE) and of leukotriene B4 (LTB4) which was rapidly metabolized into 20-OH-LTB4 and 20-COOH-LTB4. The stimulatory effect of f-Met-Leu-Phe was dose and time dependent. The tripeptide showed maximum stimulatory activity at the concentration of 1 microM and after 20-30 min of incubation. Addition of arachidonic acid to the f-Met-Leu-Phe-stimulated PMNLs resulted in an increase in the synthesis of LTB4 and 5-HETE. Pretreatment of the PMNLs with cytochalasin B strongly potentiated (up to six-fold) the stimulatory effect of f-Met-Leu-Phe on 5-lipoxygenase product synthesis, whereas cytochalasin B alone or with arachidonic acid had no significant effect. The tripeptide did not increase the synthesis of platelet-derived 12-HETE, and 12-hydroxyheptadecatrienoic acid, or of PMNL-derived 15-HETE, suggesting that its action was selective for PMNL 5-lipoxygenase. The present data indicate that f-Met-Leu-Phe causes the release of arachidonic acid from cellular lipids and activates the 5-lipoxygenase.

MeSH Terms
Arachidonic Acid Arachidonic Acids/metabolism Cytochalasin B/pharmacology Humans Hydroxyeicosatetraenoic Acids/biosynthesis Leukotriene B4/biosynthesis Lipoxygenase/metabolism N-Formylmethionine Leucyl-Phenylalanine/pharmacology Neutrophils/drug effects,metabolism
Chemicals
Arachidonic Acids Hydroxyeicosatetraenoic Acids Leukotriene B4 Arachidonic Acid Cytochalasin B 5-hydroxy-6,8,11,14-eicosatetraenoic acid N-Formylmethionine Leucyl-Phenylalanine Lipoxygenase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Salari H
Braquet P
Naccache P
Borgeat P
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30 references, click to expand
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Article Info
Journal
Inflammation
Abbr.
Inflammation
ISSN
0360-3997
DOI
10.1007/BF00917585
Published
1985-06-00
Pages
127-38
Language
English
Region
United States
NLM ID
7600105
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00917585 View journal details
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