title: Metalloproteinases shed TREM-1 ectodomain from lipopolysaccharide-stimulated human monocytes.
abstract: Triggering receptors expressed on myeloid cell (TREM) proteins are a family of cell surface receptors that participate in diverse cellular processes such as inflammation, coagulation, and bone homeostasis. TREM-1, in particular, is expressed on neutrophils and monocytes and is a potent amplifier of inflammatory responses. LPS and other microbial products induce up-regulation of cell surface-localized TREM-1 and the release of its soluble form, sTREM-1. Two hypotheses have been advanced to explain the origin of sTREM-1: alternative splicing of TREM-1 mRNA and proteolytic cleavage(s) of mature, membrane-anchored TREM-1. In this report, we present conclusive evidence in favor of the proteolytic mechanism of sTREM-1 generation. No alternative splicing forms of TREM-1 were detected in monocytes/macrophages. Besides, metalloproteinase inhibitors increased the stability of TREM-1 at the cell surface while significantly reducing sTREM-1 release in cultures of LPS-challenged human monocytes and neutrophils. We conclude that metalloproteinases are responsible for shedding of the TREM-1 ectodomain through proteolytic cleavage of its long juxtamembrane linker.
authors.affiliation: Research Unit, La Paz Hospital, Madrid, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Gómez-Piña
authors.forename: Alessandra
authors.initials: A
authors.lastname: Soares-Schanoski
authors.forename: Alexandro
authors.initials: A
authors.lastname: Rodríguez-Rojas
authors.forename: Carlos
authors.initials: C
authors.lastname: Del Fresno
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Vallejo-Cremades
authors.forename: Irene
authors.initials: I
authors.lastname: Fernández-Ruiz
authors.forename: Francisco
authors.initials: F
authors.lastname: Arnalich
authors.forename: Pablo
authors.initials: P
authors.lastname: Fuentes-Prior
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Collazo
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D001483:Base Sequence; D002478:Cells, Cultured; D006801:Humans; D006868:Hydrolysis; D008070:Lipopolysaccharides / Q000276:immunology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D045726:Metalloproteases / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009000:Monocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D012333:RNA, Messenger / Q000302:isolation & purification; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012475:Salmonella / Q000276:immunology; D012995:Solubility