title: CLEC-2 is a phagocytic activation receptor expressed on murine peripheral blood neutrophils.
abstract: CLEC-2 is a member of the "dectin-1 cluster" of C-type lectin-like receptors and was originally thought to be restricted to platelets. In this study, we demonstrate that murine CLEC-2 is also expressed by peripheral blood neutrophils, but only weakly by bone marrow or elicited inflammatory neutrophils. On circulating neutrophils, CLEC-2 can mediate phagocytosis of Ab-coated beads and the production of proinflammatory cytokines, including TNF-alpha, in response to the CLEC-2 ligand, rhodocytin. CLEC-2 possesses a tyrosine-based cytoplasmic motif similar to that of dectin-1, and we show using chimeric analyses that the activities of this receptor are dependent on this tyrosine. Like dectin-1, CLEC-2 can recruit the signaling kinase Syk in myeloid cells, however, stimulation of this pathway does not induce the respiratory burst. These data therefore demonstrate that CLEC-2 expression is not restricted to platelets and that it functions as an activation receptor on neutrophils.
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Kerrigan
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Dennehy
authors.forename: Diego
authors.initials: D
authors.lastname: Mourão-Sá
authors.forename: Inês
authors.initials: I
authors.lastname: Faro-Trindade
authors.forename: Janet A
authors.initials: JA
authors.lastname: Willment
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Eble
authors.forename: Caetano
authors.initials: C
authors.lastname: Reis e Sousa
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D016897:Respiratory Burst / Q000276:immunology; D000072377:Syk Kinase; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: C529518:CLEC-2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse