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

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          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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          Author and article information

          Journal
          Blood
          Blood
          American Society of Hematology
          0006-4971
          0006-4971
          Jun 01 2004
          : 103
          : 11
          Affiliations
          [1 ] Department of Vascular Biology and Angiogenesis Research Tumor Biology Center, Breisacher Str 117, 79106 Freiburg, Germany.
          Article
          S0006-4971(20)55408-6
          10.1182/blood-2003-10-3685
          14976056
          2bd216b4-551b-48b6-bcdf-eb979401d2a5
          History

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