A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte-specific protein 1 in human neutrophils

Taisuke Ohira, Gerard Bannenberg, Makoto Arita, Minora Takahashi, Qingyuan Ge, Thomas E. Van Dyke, Gregory L. Stahl, Charles N. Serhan, John A. Badwey

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Lipoxins and their aspirin-triggered 15-epimers are endogenous anti-inflammatory agents that block neutrophil chemotaxis in vitro and inhibit neutrophil influx in several models of acute inflammation. In this study, we examined the effects of 15-epi-16-(p-fluoro)-phenoxy-lipoxin A4 methyl ester, an aspirin-triggered lipoxin A4-stable analog (ATLa), on the protein phosphorylation pattern of human neutrophils. Neutrophils stimulated with the chemoattractant fMLP were found to exhibit intense phosphorylation of a 55-kDa protein that was blocked by ATLa (10-50 nM). This 55-kDa protein was identified as leukocyte-specific protein 1, a downstream component of the p38-MAPK cascade in neutrophils, by mass spectrometry, Western blotting, and immunoprecipitation experiments. ATLa (50 nM) also reduced phosphorylation/activation of several components of the p38-MAPK pathway in these cells (MAPK kinase 3/MAPK kinase 6, p38-MAPK, MAPK-activated protein kinase-2). These results indicate that ATLa exerts its anti-inflammatory effects, at least in part, by blocking activation of the p38-MAPK cascade in neutrophils, which is known to promote chemotaxis and other proinflammatory responses by these cells.

Original languageEnglish
Pages (from-to)2091-2098
Number of pages8
JournalJournal of Immunology
Volume173
Issue number3
Publication statusPublished - 2004 Aug 1
Externally publishedYes

Fingerprint

Aspirin
Neutrophils
Leukocytes
Phosphorylation
p38 Mitogen-Activated Protein Kinases
Proteins
Chemotaxis
Anti-Inflammatory Agents
Lipoxins
Chemotactic Factors
Mitogen-Activated Protein Kinase Kinases
Immunoprecipitation
Protein Kinases
lipoxin A4
Mass Spectrometry
Western Blotting
Inflammation

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Ohira, T., Bannenberg, G., Arita, M., Takahashi, M., Ge, Q., Van Dyke, T. E., ... Badwey, J. A. (2004). A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte-specific protein 1 in human neutrophils. Journal of Immunology, 173(3), 2091-2098.

A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte-specific protein 1 in human neutrophils. / Ohira, Taisuke; Bannenberg, Gerard; Arita, Makoto; Takahashi, Minora; Ge, Qingyuan; Van Dyke, Thomas E.; Stahl, Gregory L.; Serhan, Charles N.; Badwey, John A.

In: Journal of Immunology, Vol. 173, No. 3, 01.08.2004, p. 2091-2098.

Research output: Contribution to journalArticle

Ohira, T, Bannenberg, G, Arita, M, Takahashi, M, Ge, Q, Van Dyke, TE, Stahl, GL, Serhan, CN & Badwey, JA 2004, 'A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte-specific protein 1 in human neutrophils', Journal of Immunology, vol. 173, no. 3, pp. 2091-2098.
Ohira, Taisuke ; Bannenberg, Gerard ; Arita, Makoto ; Takahashi, Minora ; Ge, Qingyuan ; Van Dyke, Thomas E. ; Stahl, Gregory L. ; Serhan, Charles N. ; Badwey, John A. / A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte-specific protein 1 in human neutrophils. In: Journal of Immunology. 2004 ; Vol. 173, No. 3. pp. 2091-2098.
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