title: Transcellular biosynthesis of eicosanoid lipid mediators.
abstract: The synthesis of oxygenated eicosanoids is the result of the coordinated action of several enzymatic activities, from phospholipase A2 that releases the polyunsaturated fatty acids from membrane phospholipids, to primary oxidative enzymes, such as cyclooxygenases and lipoxygenases, to isomerases, synthases and hydrolases that carry out the final synthesis of the biologically active metabolites. Cells possessing the entire enzymatic machinery have been studied as sources of bioactive eicosanoids, but early on evidence proved that biosynthetic intermediates, albeit unstable, could move from one cell type to another. The biosynthesis of bioactive compounds could therefore be the result of a coordinated effort by multiple cell types that has been named transcellular biosynthesis of the eicosanoids. In several cases cells not capable of carrying out the complete biosynthetic process, due to the lack of key enzymes, have been shown to efficiently contribute to the final production of prostaglandins, leukotrienes and lipoxins. We will review in vitro studies, complex functional models, and in vivo evidences of the transcellular biosynthesis of eicosanoids and the biological relevance of the metabolites resulting from this unique biosynthetic pathway. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".
authors.affiliation: Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Valérie
authors.initials: V
authors.lastname: Capra
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: G Enrico
authors.initials: GE
authors.lastname: Rovati
authors.affiliation: Department of Experimental Medicine, Università degli Studi di Messina, Messina, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Mangano
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Carola
authors.initials: C
authors.lastname: Buccellati
authors.affiliation: Department of Pharmacology, University of Colorado at Denver, Denver, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Murphy
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; IBIM, CNR, Palermo, Italy. Electronic address: angelo.sala@unimi.it.
authors.forename: Angelo
authors.initials: A
authors.lastname: Sala
mesh_terms: D000818:Animals; D002450:Cell Communication; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D017572:Leukotriene A4 / Q000378:metabolism; D044045:Lipoxins / Q000378:metabolism; D015398:Signal Transduction; D013928:Thromboxane A2 / Q000378:metabolism
chemical_list: D015777:Eicosanoids; D017572:Leukotriene A4; D044045:Lipoxins; D004281:Docosahexaenoic Acids; D013928:Thromboxane A2; D015118:Eicosapentaenoic Acid; D011464:Epoprostenol
keywords: Arachidonic acid; Cyclooxygenases; Eicosanoids; Lipoxygenases; Transcellular biosynthesis