Critical Role of the TIE2 Endothelial Cell Receptor in the Development of Definitive Hematopoiesis

We have investigated the function of TIE2/TEK receptor tyrosine kinase in the development of definitive hematopoiesis. In the vitelline artery at 9.5 days postcoitum (d.p.c.), TIE2 + hematopoietic cells aggregated and adhered to TIE2 + endothelial cells. Soluble TIE2-Fc chimeric protein inhibited th...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 1998-11, Vol.9 (5), p.677-686
Main Authors: Takakura, Nobuyuki, Huang, Xu-Ling, Naruse, Takeshi, Hamaguchi, Isao, Dumont, Daniel J., Yancopoulos, George D., Suda, Toshio
Format: Article
Language:English
Subjects:
Angiopoietin-1
Angiopoietin-2
Animals
Blood Vessels - embryology
Cell Adhesion - physiology
Cell Line
Endothelium, Vascular - enzymology
Endothelium, Vascular - ultrastructure
Female
Fibronectins - metabolism
Hematopoiesis - physiology
Hematopoietic Stem Cells - cytology
Male
Membrane Glycoproteins - pharmacology
Membrane Glycoproteins - physiology
Mesoderm - physiology
Mice
Mice, Inbred C57BL
Proteins - pharmacology
Proteins - physiology
Proto-Oncogene Proteins c-kit - metabolism
Receptor Protein-Tyrosine Kinases - physiology
Receptor, TIE-2
Signal Transduction - physiology
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Summary:We have investigated the function of TIE2/TEK receptor tyrosine kinase in the development of definitive hematopoiesis. In the vitelline artery at 9.5 days postcoitum (d.p.c.), TIE2 + hematopoietic cells aggregated and adhered to TIE2 + endothelial cells. Soluble TIE2-Fc chimeric protein inhibited the development of hematopoiesis and angiogenesis in the para-aortic splanchnopleural mesoderm (P-Sp) explant culture, and TIE2-deficient mice showed severely impaired definitive hematopoiesis. An in vitro study revealed that Angiopoietin-1 but not Angiopoietin-2 promoted the adhesion to fibronectin (FN) through integrins in TIE2-transfected cells and primary TIE2 + cells sorted from 9.5 d.p.c. P-Sp. Adhesion of TIE2 + cells induced by Angiopoietin-1 enhanced the proliferation of hematopoietic progenitor cells.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(00)80665-2