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CUTTING EDGE |
*
Centre for Molecular Inflammation and Vascular Research, Mater Misericordiae Hospital and Department of Medicine and Therapeutics, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland;
Department of Chemistry, University of Southern California, Los Angeles, CA 90089; and
Imperial Cancer Research Fund, London, United Kingdom
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 (M
). 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,
vß3, 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 M. 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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C. Bonnans, I. Vachier, C. Chavis, P. Godard, J. Bousquet, and P. Chanez Lipoxins Are Potential Endogenous Antiinflammatory Mediators in Asthma Am. J. Respir. Crit. Care Med., June 1, 2002; 165(11): 1531 - 1535. [Abstract] [Full Text] [PDF]
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M. O. Leonard, K. Hannan, M. J. Burne, D. W. P. Lappin, P. Doran, P. Coleman, C. Stenson, C. T. Taylor, F. Daniels, C. Godson, et al. 15-Epi-16-(Para-Fluorophenoxy)-Lipoxin A4-Methyl Ester, a Synthetic Analogue of 15-epi-Lipoxin A4, Is Protective in Experimental Ischemic Acute Renal Failure J. Am. Soc. Nephrol., June 1, 2002; 13(6): 1657 - 1662. [Abstract] [Full Text] [PDF]
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P. Maderna, D. C. Cottell, G. Berlasconi, N. A. Petasis, H. R. Brady, and C. Godson Lipoxins Induce Actin Reorganization in Monocytes and Macrophages But Not in Neutrophils : Differential Involvement of Rho GTPases Am. J. Pathol., June 1, 2002; 160(6): 2275 - 2283. [Abstract] [Full Text] [PDF]
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J. Goh, A. W. Baird, C. O'Keane, R. W. G. Watson, D. Cottell, G. Bernasconi, N. A. Petasis, C. Godson, H. R. Brady, and P. MacMathuna Lipoxin A4 and Aspirin-Triggered 15-Epi-Lipoxin A4 Antagonize TNF-{alpha}-Stimulated Neutrophil-Enterocyte Interactions In Vitro and Attenuate TNF-{alpha}-Induced Chemokine Release and Colonocyte Apoptosis in Human Intestinal Mucosa Ex Vivo J. Immunol., September 1, 2001; 167(5): 2772 - 2780. [Abstract] [Full Text] [PDF]
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M. THURNHER, C. ZELLE-RIESER, R. RAMONER, G. BARTSCH, and L. HOLTL The disabled dendritic cell FASEB J, April 1, 2001; 15(6): 1054 - 1061. [Abstract] [Full Text] [PDF]
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B. McMahon, C. Stenson, F. McPhillips, A. Fanning, H. R. Brady, and C. Godson Lipoxin A4 Antagonizes the Mitogenic Effects of Leukotriene D4 in Human Renal Mesangial Cells. DIFFERENTIAL ACTIVATION OF MAP KINASES THROUGH DISTINCT RECEPTORS J. Biol. Chem., September 1, 2000; 275(36): 27566 - 27575. [Abstract] [Full Text] [PDF]
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