Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages.

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.
AuthorsC Godson, S Mitchell, K Harvey, N A Petasis, N Hogg, H R Brady
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 164 Issue 4 Pg. 1663-7 (Feb 15 2000) ISSN: 0022-1767 [Print] UNITED STATES
PMID10657608 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Hydroxyeicosatetraenoic Acids
  • Lipoxins
  • lipoxin A4
  • Cyclic AMP-Dependent Protein Kinases
  • 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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