Lipoxin and aspirin-triggered 15-epi-lipoxin cellular interactions anti-inflammatory lipid mediators.
Eicosanoids are known to play important roles in inflammation. Recent findings have given rise to several new concepts regulating the generation of eicosanoids, illustrated in Figure 1. Lipoxins (LX) are trihydroxytetraene-containing eicosanoids that are generated within vascular lumen by platelet-leukocyte interactions and at mucosal surfaces by leukocyte-epithelial cell interactions. During these cell-cell interactions, transcellular biosynthetic pathways are used as major routes, and thus, in humans, LX are formed in vivo during multicellular responses such as inflammation, atherosclerosis, and thrombosis. This branch of the eicosanoid cascade generates specific tetraene-containing products that appear to function as stop signals, since they inhibit key steps in leukocyte-mediated inflammation. Of special interest, it appears that aspirin also functions in part via production of novel epimers of lipoxins or 15-epi-lipoxins (Figure 1). Here, we review recent developments on the cellular interactions of these novel anti-inflammatory mediators.
Serhan
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Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. cnserhan@zeus.bwh.harvard.edu
Takano
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Gronert
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Chiang
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Clish
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D000595:Amino Acid Sequence; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D003872:Dermatitis / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D044045:Lipoxins; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D017386:Sequence Homology, Amino Acid
C105101:FPR2 protein, human; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C040527:lipoxin A4; D001241:Aspirin