title: Interaction of S100A8/S100A9-arachidonic acid complexes with the scavenger receptor CD36 may facilitate fatty acid uptake by endothelial cells.
abstract: Recently, we showed that S100A8/A9 were secreted from phorbol ester-stimulated neutrophil-like HL-60 cells, thereby carrying arachidonic acid [Kerkhoff et al. (1999) J. Biol. Chem. 274, 32672-32679]. The present study was undertaken to evaluate whether the secreted S100A8/A9-AA complex might be involved in transcellular eicosanoid metabolism. In the presence of S100A8/A9, arachidonic acid was rapidly taken up by human umbilical vein endothelial cells in a saturable and energy-dependent fashion. Protein-facilitated arachidonate uptake was confirmed by its sensitivity toward the protein modifiers bromobimane and phloretin. Both potassium and sodium depletion did not affect the arachidonate transport, indicating that arachidonate influx was independent of endocytosis. The uptake of exogenous arachidonic acid by HUVEC was predominantly mediated by FAT/CD36. This conclusion was drawn by the findings that (i) arachidonate uptake was drastically inhibited by sulfo-N-succinimidyl oleate, a specific inhibitor of FAT/CD36; (ii) the maximal inhibition of arachidonate uptake induced by SSO was similar to that effected by ATP depletion; and (iii) the arachidonate transport was 2-fold higher in COS-7 cells transfected with the pEF.BOS-CD36 expression vector than in the empty vector-transfected COS-7 cells. Kinetic studies of arachidonate uptake were indicative for an interaction between fatty acid transporter and S100A8/A9-AA complex that was confirmed by an in vitro protein-protein interaction assay. FAT/CD36 has been suggested to be involved in inflammatory responses, and S100A8/A9 are released from activated leukocytes at inflammatory loci. Therefore, it can be envisioned that their interaction might propagate host response by perpetuating recruitment and activation of cellular effectors.
authors.affiliation: Institute of Experimental Dermatology, D-48149 Münster, Germany. kerkhoc@uni-muenster.de
authors.forename: C
authors.initials: C
authors.lastname: Kerkhoff
authors.forename: C
authors.initials: C
authors.lastname: Sorg
authors.forename: N N
authors.initials: NN
authors.lastname: Tandon
authors.forename: W
authors.initials: W
authors.lastname: Nacken
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019556:COS Cells; D040502:Calgranulin B; D002352:Carrier Proteins / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005228:Fatty Acids, Essential / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009829:Oleic Acids / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D051122:Scavenger Receptors, Class B; D013388:Succinimides / Q000494:pharmacology; D014162:Transfection; D025521:Tumor Suppressor Proteins
chemical_list: D000943:Antigens, Differentiation; D018955:CD36 Antigens; D040502:Calgranulin B; D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005228:Fatty Acids, Essential; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009829:Oleic Acids; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D009418:S100 Proteins; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D013388:Succinimides; D025521:Tumor Suppressor Proteins; C120556:sulfo-N-succinimidyl oleate; D016718:Arachidonic Acid