Linked Life Data

12239238

Source:http://linkedlifedata.com/resource/pubmed/id/12239238

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2002-9-19
pubmed:abstractText
Lipoxins (LX) are eicosanoids with antiinflammatory activity in glomerulonephritis (GN) and inflammatory diseases, hypersensitivity, and ischemia reperfusion injury. It has been demonstrated that LXA(4) stimulates non-phlogistic phagocytosis of apoptotic polymorphonuclear neutrophils (PMN) by monocyte-derived macrophages (Mphi) in vitro, suggesting a role for LX as endogenous pro-resolution lipid mediators. It is here reported that LXA(4), LXB(4), the aspirin-triggered LX (ATL) epimer, 15-epi-LXB(4), and a stable synthetic analogue 15(R/S)-methyl-LXA(4) stimulate phagocytosis of exogenously administered excess apoptotic PMN by macrophages (M phi) in vivo in a classic model of acute inflammation, namely thioglycollate-induced peritonitis. Significant enhancement of phagocytosis in vivo was observed with 15-min exposure to LX and with intraperitoneal doses of LXA(4), LXB(4), 15(R/S)-methyl-LXA(4), and 15-epi-LXB(4) of 2.5 to 10 micro g/kg. Non-phlogistic LX-stimulated phagocytosis by M phi was sensitive to inhibition of PKC and PI 3-kinase and associated with increased production of transforming growth factor-beta(1) (TGF-beta(1)). LX-stimulated phagocytosis was not inhibited by phosphatidylserine receptor (PSR) antisera and was abolished by prior exposure of M phi to beta 1,3-glucan, suggesting a novel M phi-PMN recognition mechanism. Interestingly, the recently described peptide agonists of the LXA(4) receptor (MYFINITL and LESIFRSLLFRVM) stimulated phagocytosis through a process associated with increased TGF-beta(1) release. These data provide the first demonstration that LXA(4), LXB(4), ATL, and LX stable analogues rapidly promote M phi phagocytosis of PMN in vivo and support a role for LX as rapidly acting, pro-resolution signals in inflammation. Engagement of the LXR by LX generated during cell-cell interactions in inflammation and by endogenous LXR peptide agonists released from distressed cells may be an important stimulus for clearance of apoptotic cells and may be amenable to pharmacologic mimicry for therapeutic gain.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1046-6673
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2497-507
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12239238-Anti-Inflammatory Agents, pubmed-meshheading:12239238-Apoptosis, pubmed-meshheading:12239238-Aspirin, pubmed-meshheading:12239238-Bone Marrow, pubmed-meshheading:12239238-Cells, Cultured, pubmed-meshheading:12239238-Cyclic AMP, pubmed-meshheading:12239238-Drug Stability, pubmed-meshheading:12239238-Eicosanoids, pubmed-meshheading:12239238-Enzymes, pubmed-meshheading:12239238-Humans, pubmed-meshheading:12239238-Inflammation, pubmed-meshheading:12239238-Jumonji Domain-Containing Histone Demethylases, pubmed-meshheading:12239238-Lipids, pubmed-meshheading:12239238-Macrophages, pubmed-meshheading:12239238-Neutrophils, pubmed-meshheading:12239238-Peptides, pubmed-meshheading:12239238-Phagocytosis, pubmed-meshheading:12239238-Phenotype, pubmed-meshheading:12239238-Receptors, Cell Surface
pubmed:year
2002
pubmed:articleTitle
Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the resolution of inflammation: stimulation of macrophage phagocytosis of apoptotic neutrophils in vivo.
pubmed:affiliation
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, Ireland.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't