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Dual role of lipoxin A4 in pneumosepsis pathogenesis.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2013 Oct; Vol. 17 (2), pp. 283-92. Date of Electronic Publication: 2013 Jun 28. - Publication Year :
- 2013
-
Abstract
- Lipoxin A4 (LXA4) is an endogenous lipid mediator with potent anti-inflammatory actions but its role in infectious processes is not well understood. We investigated the involvement of LXA4 and its receptor FPR2/ALX in the septic inflammatory dysregulation. Pneumosepsis was induced in mice by inoculation of Klebsiella pneumoniae. LXA4 levels and FPR2/ALX expression in the infectious focus as well as the effects of treatment with receptor agonists (LXA4 and BML-111) and antagonists (BOC-2 and WRW(4)) in early (1h) and late (24h) sepsis were studied. Sepsis induced an early increase in LXA4, FPR2/ALX lung expression, local and systemic infection and inflammation, and mortality. Treatment with BOC-2 in early sepsis increased leukocyte migration to the focus, and reduced bacterial load and dissemination. Inhibition of 5- and 15-lipoxygenase in early sepsis also increased leukocyte migration. Early treatment with WRW(4) and BOC-2 improved survival. Treatment with authentic LXA4 or BML-111 in early sepsis decreased cell migration and worsened the infection. In late sepsis, treatment with BOC-2 had no effect, but LXA4 improved the survival rate by reducing the excessive inflammatory response, this effect being abolished by pretreatment with BOC-2. Thus, the anti-inflammatory and pro-resolution mediator LXA4 and its receptor FPR2/ALX levels were increased in the early phase of sepsis, contributing to the septic inflammatory dysregulation. In addition, LXA4 has a dual role in sepsis and that its beneficial or harmful effects are critically dependent on the time. Therefore, a proper interference with LXA4 system may be a new therapeutic avenue to treat sepsis.<br /> (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Bacterial Load drug effects
Cell Movement drug effects
Cells, Cultured
Disease Progression
Heptanoic Acids administration & dosage
Heptanoic Acids pharmacology
Interleukin-1beta blood
Klebsiella Infections complications
Lipoxins administration & dosage
Lipoxins immunology
Lung drug effects
Lung microbiology
Male
Mice
Oligopeptides administration & dosage
Oligopeptides pharmacology
Receptors, Formyl Peptide agonists
Receptors, Formyl Peptide antagonists & inhibitors
Sepsis etiology
Tumor Necrosis Factor-alpha blood
Klebsiella Infections immunology
Klebsiella pneumoniae immunology
Lipoxins metabolism
Lung immunology
Sepsis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 17
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 23816538
- Full Text :
- https://doi.org/10.1016/j.intimp.2013.06.010