Novel roles for podocalyxin in regulating stress myelopoiesis, Rap1a, and neutrophil migration.

Document Type

Article

Publication Date

6-1-2017

Institution/Department

MMCRI; Molecular Medicine

Journal Title

Experimental hematology.

MeSH Headings

Animals, Gene Expression Profiling, Gene Expression Regulation, Gene Order, Genetic Loci, Granulocyte Colony-Stimulating Factor, Hematopoietic Stem Cells, Humans, Mice, Mice, Knockout, Myelopoiesis, Neutrophils, Sialoglycoproteins, Stress, Physiological, rap1 GTP-Binding Proteins

Abstract

Podocalyxin (Podxl) is a CD34 orthologue and cell surface sialomucin reported to have roles in renal podocyte diaphragm slit development; vascular cell integrity; and the progression of blood, breast, and prostate cancers. Roles for Podxl during nonmalignant hematopoiesis, however, are largely undefined. We have developed a Vav-Cre Podxl knockout (KO) mouse model, and report on novel roles for Podxl in governing stress myelopoiesis. At steady state, Podxl expression among hematopoietic progenitor cells was low level but was induced by granulocyte colony-stimulating factor (G-CSF) in myeloid progenitors and by thrombopoietin in human stem cells. In keeping with low-level Podxl expression at steady state, Vav-Cre deletion of Podxl did not markedly alter peripheral blood cell levels. A G-CSF challenge in Podxl-KO mice, in contrast, hyperelevated peripheral blood neutrophil and monocyte levels. Podxl-KO also substantially heightened neutrophil levels after 5-fluorouracil myeloablation. These loss-of-function phenotypes were selective, and Podxl-KO did not alter lymphocyte, basophil, or eosinophil levels. Within bone marrow (and after G-CSF challenge), Podxl deletion moderately decreased colony forming units-granulocytes, eyrthrocytes, monocyte/macrophages, megakaryocytes and CD16/32

ISSN

1873-2399

First Page

77

Last Page

83

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