Lipoxin

Lipoxin

Chembox new
Name = Lipoxin B4
ImageFile = Lipoxin B4.svg
ImageSize = 200px
ImageName = Lipoxin B4
IUPACName=5S,14R,15S-Trihydroxy-6E,8Z,10E,12E -eicosatetraenoic acid
OtherNames=LXB4
Section1= Chembox Identifiers
CASNo=92950-25-9
PubChem=5280915
SMILES=CCCCCC(C(C=CC=CC=CC=CC(CCCC(=O)O)O)O)O

Section2= Chembox Properties
Formula=C20H32O5
MolarMass=352.46508 g/mol

Lipoxins are a series of anti-inflammatory mediators. Lipoxins are short lived endogenously produced nonclassic eicosanoids whose appearance in inflammation signals the resolution of inflammation. They are abbreviated as LX, an acronym for lipoxygenase (LO) interaction products. At present two lipoxins have been identified; lipoxin A4 (LXA4) and lipoxin B4 (LXB4).

History

Lipoxins were first described by Serhan, Hamberg and
Samuelsson in 1984. They reported that the lipoxins stimulated superoxide anion (O2) generation and degranulation at submicromolar concentrations—as potent as LTB4.

Biosynthesis

Lipoxins are derived enzymatically from arachidonic acid, an ω-6 fatty acid. An analogous class, the resolvins, is derived from EPA and DHA, ω-3 fatty acids.cite web
url=http://www.pnas.org/cgi/content/abstract/81/17/5335
title=Lipoxins: Novel Series of Biologically Active Compounds Formed from Arachidonic Acid in Human Leukocytes
url=http://www.pnas.org/cgi/reprint/81/17/5335 |format=pdf
author=Charles N. Serhan, Mats Hamberg, and Bengt Samuelsson
date=September 1, 1984| accessdate = 2006-02-02
Original description of lipoxins.] Another analogous class, the epi-lipoxins, is formed by non-enzymatic peroxidation.

Biological activity

Lipoxins, as well as certain peptides, are high affinity ligands for the lipoxin A4 receptor (LXA4R), which was first identified based on sequence homology as the formyl peptide receptor like receptor (FPRL1). Lipoxin signaling through the LXA4R inhibits chemotaxis, transmigration, superoxide generation and NF-κB activation.cite web |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16125378&query_hl=8&itool=pubmed_docsum | title=Anti-inflammatory circuitry: Lipoxin, aspirin-triggered lipoxins and their receptor ALX | author= Chiang N., Arita M., and Serhan CN. | publishdate= Prostaglandins, Leukotrienes and Essential Fatty Acids 73 (2005) 163-177 | year=2005 | accessdate = 2006-04-28 ]

Conversely, peptide signaling through the same receptor, in vitro, has been shown to stimulate chemotaxis of polymorphonuclear cells (PMNs) and calcium mobilization. The peptides that have ALXR affinity tend to be signals for leukocyte migration and subsequent phagocytosis such as acute phase proteins, bacterial peptides, HIV envelope proteins and neurotoxic peptides.

Similarly to the leukotrienes, LXA4 will form the cysteinyl-lipoxins LXC4, LXD4 and LXE4.cite journal |author=Powell WS, Chung D, Gravel S |title=5-Oxo-6,8,11,14-eicosatetraenoic acid is a potent stimulator of human eosinophil migration |journal=J. Immunol. |volume=154 |issue=8 |pages=4123–32 |year=1995 |pmid=7706749 |doi=] At subnanomolar concentrations, LXA4 and LXB4 inhibit leukotriene-stimulated interactions of human neutrophils and endothelial cells.cite journal
author=Papayianni A, Serhan CN, Brady HR
title=Lipoxin A4 and B4 inhibit leukotriene-stimulated interactions of human neutrophils and endothelial cells
journal=J. Immunol.
volume=156
issue=6
pages=2264–72
year=1996
pmid=8690917
doi=
accessdate=2007-11-01
]

Lipoxins are high affinity antagonists to the cysteinyl leukotriene receptor type 1 (CysLT1) to which several leukotrienes (LTC4, LTD4 and LTE4) mediate their smooth muscle contraction and eosinophil chemotactic effects. The CysLT1 receptor is also the site of action for the asthma drug montelukast (Singulair).cite journal | pmid = 9895400
author= Drazen J., Israel E., and O'Byrne P.
title= Treatment of Asthma with Drugs Modifying the Leukotriene Pathway | publishdate= N Engl J Med. 1999 January 21;340(3):197-206 | year=1999 | accessdate= 2006-04-28
]

In resolution

During inflammation, cells die by apoptosis. As part of resolution, lipoxins signal macrophages to the remains of these cells (phagocytosis).cite journal |author=Mitchell S, Thomas G, Harvey K, "et al" |title=Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the resolution of inflammation: stimulation of macrophage phagocytosis of apoptotic neutrophils in vivo |journal=J. Am. Soc. Nephrol. |volume=13 |issue=10 |pages=2497–507 |year=2002 |pmid=12239238 |doi=10.1097/01.ASN.0000032417.73640.72] During the acute inflammatory process, the proinflammatory cytokines such as IFN-γ and IL-1β can induce the expression of anti-inflammatory mediators such as lipoxins and IL-4, which promote the resolution phase of inflammation.cite web
url= http://ajprenal.physiology.org/cgi/content/full/286/2/F189
title=Lipoxins: endogenous regulators of inflammation
author= McMahon, Blaithin and Godson, Catherine
publishdate=Am J Physiol Renal Physiol 286: F189-F201, 2004
accessdate = 2006-02-07
Invited review article.]

Lipoxin analogues

Stable synthetic analogues of LXs and aspirin-triggered 15-epi-LXA4s (ATLs) can mimic many of the desirable anti-inflammatory, "pro-resolution" actions of native LXs.cite journal |author=McMahon B, Mitchell S, Brady HR|title=Lipoxins: revelations on resolution |journal=Trends Pharmacol. Sci. |volume=22 |issue=8 |pages=391–5 |year=2001 |pmid=11478982 | doi= 10.1016/S0165-6147(00)01771-5 ]

References

External links

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