Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages.
TL;DR: It is suggested 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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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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Citations
Lipoxins: regulators of resolution
Aidan Ryan,Catherine Godson +1 more
TL;DR: There is accumulating evidence that LXs are potential therapeutic agents for inflammatory disorders leading to tissue damage and organ fibrosis.
Lipoxin Mimetics and the Resolution of Inflammation.
TL;DR: In this paper , the authors discuss the potential of arachidonate-derived lipoxins in self-limiting inflammatory responses to promote the resolution of inflammation and endogenous repair mechanisms without compromising host defense.
LXA4 stimulates ZO-1 expression and transepithelial electrical resistance in human airway epithelial (16HBE14o-) cells
TL;DR: Evidence is provided that LXA(4) plays certainly a new role for the regulation of tight junction formation and stimulation of the localization and expression of ZO-1 at the plasma membrane through a mechanism involving the LXA (4) receptor.
Anti-inflammatory and pro-resolving properties of benzo-lipoxin A4 analogs
Yee-Ping Sun,Eric Tjonahen,Raquel Keledjian,Min Zhu,Rong Yang,Rong Yang,Antonio Recchiuti,Padmini S. Pillai,Nicos A. Petasis,Charles N. Serhan +9 more
TL;DR: A new generation of LXA(4) stable analogs that are easy to synthesize and anti-inflammatory are demonstrated and are promising tools for new therapeutic approaches as well as assessing endogenous mechanisms in anti-inflammation and resolution.
Lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 inhibit peroxynitrite formation, NF-kappa B and AP-1 activation, and IL-8 gene expression in human leukocytes
TL;DR: It is suggested that by attenuating ONOO− formation, LXA4 and ATL can oppose OnOO− signaling in leukocytes and provide a rationale for using stable synthetic analogues as antiinflammatory compounds in vivo.
References
Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.
TL;DR: The results suggest that binding and/or phagocytosis of apoptotic cells induces active antiinflammatory or suppressive properties in human macrophages, likely that resolution of inflammation depends not only on the removal of apoptosis but on active suppression of inflammatory mediator production.
Human CD14 mediates recognition and phagocytosis of apoptotic cells
Andrew Devitt,Andrew Devitt,Odette D. Moffatt,Odette D. Moffatt,Chandra Raykundalia,J. Donald Capra,David Simmons,Christopher D. Gregory,Christopher D. Gregory +8 more
TL;DR: Results indicate that clearance of apoptotic cells is mediated by a receptor whose interactions with ‘non-self’ components (LPS) and ‘self” components (apoptotic cells) produce distinct macrophage responses.
Aspirin-triggered 15-Epi-Lipoxin A4 (LXA4) and LXA4 Stable Analogues Are Potent Inhibitors of Acute Inflammation: Evidence for Anti-inflammatory Receptors
TL;DR: In this article, a mouse LXA4 receptor (LXA4R) was cloned and characterized in Chinese hamster ovary cells and showed specific binding to [3H]LXAsa4 (K d ≈ 1.5 nM), and with LXa4 activated GTP hydrolysis.
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Design of lipoxin A4 stable analogs that block transmigration and adhesion of human neutrophils.
Charles N. Serhan,Jane F. Maddox,Nicos A. Petasis,Irini Akritopoulou-Zanze,Aikaterina Papayianni,Hugh R. Brady,Sean P. Colgan,James L. Madara +7 more
TL;DR: Lipoxins are bioactive eicosanoids that carry a tetraene structure and serve as regulators of inflammation, in part by inhibiting neutrophil migration and adhesion and the results suggest that LXA4 stable analogs can be useful tools both in vitro and in vivo to evaluate LXA 4 actions and therapeutic potential.
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Recognition and phagocytosis of cells undergoing apoptosis
TL;DR: A full understanding of this complexity will require definition of recognition mechanisms which operate in vivo in higher organisms as well as specific evidence in vitro for involvement of phagocyte receptors.