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The Tie-2 ligand Angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies

Open access
Fiedler, Ulrike, Scharpfenecker, Marion, Koidl, Stefanie, Hegen, Anja, Grunow, Verena, Schmidt, Jarno M., Kriz, Wilhelm, Thurston, Gavin, Augustin, Hellmut G.·2004·Blood

Abstract

The angiopoietins Ang-1 and Ang-2 have been identified as ligands with opposing functions of the receptor tyrosine kinase Tie-2 regulating endothelial cell survival and vascular maturation. Ang-1 acts in a paracrine agonistic manner, whereas Ang-2 appears to act primarily as an autocrine antagonistic regulator. To shed further light on the complexity of autocrine/paracrine agonistic/antagonistic functions of the angiopoietin/Tie-2 system, we have studied Ang-2 synthesis and secretion in different populations of wild-type and retrovirally Ang-2–transduced endothelial cells. Endogenous and overexpressed endothelial cell Ang-2 is expressed in a characteristic granular pattern indicative of a cytoplasmic storage granule. Light and electron microscopic double staining revealed Ang-2 colocalization with von Willebrand factor, identifying Ang-2 as a Weibel-Palade body molecule. Costaining with P-selectin showed that storage of Ang-2 and P-selectin in Weibel-Palade bodies is mutually exclusive. Stored Ang-2 has a long half-life of more than 18 hours and can be secreted within minutes of stimulation (eg, by phorbol 12-myristate 13-acetate [PMA], thrombin, and histamine). Collectively, the identification of Ang-2 as a stored, rapidly available molecule in endothelial cells strongly suggests functions of the angiopoietin/Tie-2 system beyond the established roles during angiogenesis likely to be involved in rapid vascular homeostatic reactions such as inflammation and coagulation.

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Metadata

Authors
Fiedler, U., Scharpfenecker, M., Koidl, S., Hegen, A., Grunow, V., Schmidt, J. M., Kriz, W., Thurston, G., & Augustin, H. G.
Venue
Blood
Published
2004-06-01
Volume
103
Issue
11
Pages
4150-4156
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2042350316
Cited by
742
References
43
FWCI
5.25
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: The Tie-2 ligand Angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. https://app.cochat.ai/papers/10.1182/blood-2003-10-3685
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Fiedler, U., Scharpfenecker, M., Koidl, S., Hegen, A., Grunow, V., Schmidt, J. M., Kriz, W., Thurston, G., & Augustin, H. G. (2004). The Tie-2 ligand Angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood. https://doi.org/10.1182/blood-2003-10-3685

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