Abstract |
Lipoxins (LX) are lipoxygenase-derived eicosanoids generated during inflammation. LX inhibit polymorphonuclear neutrophil (PMN) chemotaxis and adhesion and are putative braking signals for PMN-mediated tissue injury. In this study, we report that LXA4 promotes another important step in the resolution phase of inflammation, namely, phagocytosis of apoptotic PMN by monocyte-derived macrophages (Mphi). LXA4 triggered rapid, concentration-dependent uptake of apoptotic PMN. This bioactivity was shared by stable synthetic LXA4 analogues (picomolar concentrations) but not by other eicosanoids tested. LXA4-triggered phagocytosis did not provoke IL-8 or monocyte chemoattractant protein-1 release. LXA4-induced phagocytosis was attenuated by anti-CD36, alphavbeta3, and CD18 mAbs. LXA4-triggered PMN uptake was inhibited by pertussis toxin and by 8-bromo-cAMP and was mimicked by Rp-cAMP, a protein kinase A inhibitor. LXA4 attenuated PGE2-stimulated protein kinase A activation in Mphi. These results suggest that LXA4 is an endogenous stimulus for PMN clearance during inflammation and provide a novel rationale for using stable synthetic analogues as anti-inflammatory compounds in vivo.
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Authors | C Godson, S Mitchell, K Harvey, N A Petasis, N Hogg, H R Brady |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 164
Issue 4
Pg. 1663-7
(Feb 15 2000)
ISSN: 0022-1767 [Print] United States |
PMID | 10657608
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Hydroxyeicosatetraenoic Acids
- Lipoxins
- lipoxin A4
- Cyclic AMP-Dependent Protein Kinases
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Topics |
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology)
- Apoptosis
(immunology)
- Cell Adhesion
(immunology)
- Cyclic AMP-Dependent Protein Kinases
(antagonists & inhibitors, metabolism)
- Dose-Response Relationship, Immunologic
- Humans
- Hydroxyeicosatetraenoic Acids
(physiology)
- Lipoxins
- Macrophages
(immunology)
- Molecular Mimicry
- Monocytes
(immunology)
- Neutrophils
(cytology, enzymology, immunology)
- Phagocytosis
(immunology)
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