Ligation of CD200R by CD200 is not required for normal murine myelopoiesis.
CD200R is an inhibitory receptor involved in the regulation of myeloid cells. It recruits Dok-1 and Dok-2, which are potent inhibitors of the Ras signalling pathway used by colony-stimulating factor (CSF) receptors. Dok-1/Dok-2 double knockout (DKO) mice develop leukaemia at 10-12 months of age. We investigated whether disturbed CD200R signalling could be responsible for this phenotype. Therefore, we studied whether CD200(-/-) mice have altered myelopoiesis and develop leukaemia. We report that CD200R is expressed on haematopoietic progenitor cells. However, CD200(-/-) mice have normal numbers of myeloid progenitors in the bone marrow and these cells have normal proliferative capacity. These results indicate that the development of leukaemia in Dok-1/Dok-2 DKO mice is not solely due to an absence of CD200R signalling. In addition, we show that the previously reported enhanced numbers of myeloid cells do not occur in all CD200(-/-) mice. We determined whether variations in the numbers of peripheral myeloid cells were due to an enhanced response to granulocyte-CSF (G-CSF) or an inflammatory stimulus. Mobilisation of immature neutrophils via G-CSF and infiltration of mature neutrophils and macrophages upon thioglycolate injection were not altered in CD200(-/-) mice. We conclude that CD200(-/-) mice exhibit normal myelopoiesis and that development of leukaemia in Dok-1/Dok-2 DKO mice is not caused by a lack of CD200-mediated CD200R signalling.
Rijkers
Eva S K
ES
Department of Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
de Ruiter
Talitha
T
Buitenhuis
Miranda
M
Veninga
Henrike
H
Hoek
Robert M
RM
Meyaard
Linde
L
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor; D007938:Leukemia / Q000378:metabolism* / Q000503:physiopathology; D008264:Macrophages; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023461:Myeloid Progenitor Cells / Q000378:metabolism; D038042:Myelopoiesis; D009504:Neutrophils; D010641:Phenotype; D010750:Phosphoproteins / Q000172:deficiency; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D013864:Thioglycolates / Q000008:administration & dosage