当前位置： SCI文献检索 > BLOOD期刊下所有文献 > Lineage-specific growth factors can compensate for stem and progenitor cell deficiencies at the postprogenitor cell level: an analysis of doubly TPO- and G-CSF receptor-deficient mice.

Lineage-specific growth factors can compensate for stem and progenitor cell deficiencies at the postprogenitor cell level: an analysis of doubly TPO- and G-CSF receptor-deficient mice.

Abstract：

:Multiple lines of evidence indicate that thrombopoietin (TPO) substantially impacts the number of hematopoietic stem cells and progenitors of all myeloid lineages. Nevertheless, tpo knock-out mice (T(-)) display thrombocytopenia only; blood erythroid and neutrophil levels are normal despite 60% to 85% reductions in stem and progenitor cells. The compensatory mechanism(s) for these deficiencies remains uncertain; lineage-specific cytokines such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) have been postulated but never proven to be responsible. To directly test whether G-CSF can compensate for the myeloid progenitor cell reduction in the T(-) model of hematopoietic deficiency, T(-) and G-CSF-receptor knock-out (GR(-)) mice were crossed, and F1 animals bred to obtain doubly nullizygous mice (T(-)GR(-)). This experiment also allowed us to test the hypothesis that G-CSF contributes to the residual platelet production in T(-) mice. We found that T(-)GR(-) F2 mice displayed similar blood platelet levels as that seen in T(-) mice, indicating that G-CSF does not account for the residual megakaryopoiesis in T(-) mice. However, we also noted excessive perinatal mortality of T(-)GR(-) animals, caused by infection due to a profound and significant decrease in marrow and peripheral blood neutrophils, far greater than that seen in either T(-) or GR(-) mice. These data indicate that in the additional absence of GR, T(-) mice cannot compensate for their 62% reduction in myeloid progenitors and become profoundly neutropenic, supporting the hypothesis that G-CSF can compensate for the myeloid effects of TPO deficiency by expanding the pool of cells between the granulocyte-macrophage colony-forming unit and mature neutrophil stages of granulopoiesis.

journal_name

Blood

journal_title

Blood

authors

Kaushansky K,Fox N,Lin NL,Liles WC

doi

10.1182/blood.v99.10.3573

subject

Has Abstract

pub_date

2002-05-15 00:00:00

pages

3573-8

issue

eissn

0006-4971

issn

1528-0020

journal_volume

pub_type

杂志文章

在线工具

Lineage-specific growth factors can compensate for stem and progenitor cell deficiencies at the postprogenitor cell level: an analysis of doubly TPO- and G-CSF receptor-deficient mice.