CLEC-2 is a phagocytic activation receptor expressed on murine peripheral blood neutrophils.
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.
Kerrigan
Ann M
AM
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
Dennehy
Kevin M
KM
Mourão-Sá
Diego
D
Faro-Trindade
Inês
I
Willment
Janet A
JA
Taylor
Philip R
PR
Eble
Johannes A
JA
Reis e Sousa
Caetano
C
Brown
Gordon D
GD
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
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