Ligation of CD200R by CD200 is not required for normal murine myelopoiesis.

Abstract:

: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.

journal_name

Eur J Haematol

authors

Rijkers ES,de Ruiter T,Buitenhuis M,Veninga H,Hoek RM,Meyaard L

doi

10.1111/j.1600-0609.2007.00920.x

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

410-6

issue

5

eissn

0902-4441

issn

1600-0609

pii

EJH920

journal_volume

79

pub_type

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