The adaptor protein p66shc is a positive regulator in the angiogenic response induced by hypoxic T cells

Journal of Leukocyte Biology

Michela Pellegrini²  Domenico Ribatti³  Marco Presta⁴  Fabio Carraro⁵  Antonella Naldini⁵  Emilia Morena⁵  Annalisa Pucci⁵  Cosima T. Baldari²  Pier Giuseppe Pelicci¹ 

[1] European Institute of Oncology, Milano, Italy; European Institute of Oncology, Milano, Italy; European Institute of Oncology, Milano, Italy;Department of Evolutionary Biology, University of Siena, Siena, Italy; Department of Evolutionary Biology, University of Siena, Siena, Italy; Department of Evolutionary Biology, University of Siena, Siena, Italy;;Department of Human Anatomy and Histology, University of Bari, Bari, Italy Department of Human Anatomy and Histology, University of Bari, Bari, Italy Department of Human Anatomy and Histology, University of Bari, Bari, Italy;Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy; and Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy; and Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy; and;Unit of Neuroimmunophysiology, Department of Physiology, and Unit of Neuroimmunophysiology, Department of Physiology, and Unit of Neuroimmunophysiology, Department of Physiology, and

关键词: T lymphocytes;    inflammation;    cytokines;   

DOI  :  10.1189/jlb.0709460

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Immune cells play an important role in the onset of angiogenesis. Here, we report that VEGF represents the major proangiogenic factor expressed by T cells exposed to hypoxia, a common feature of inflammation and tumor microenvironment. The supernatants of hypoxic T cells were highly angiogenic when delivered on the chick embryo CAM. The angiogenic response was abrogated by a neutralizing anti-VEGF antibody and mimicked by rVEGF. Interestingly, VEGF induction by hypoxia was up-regulated in Jurkat T cells overexpressing the adaptor protein p66Shc but not the inactive S36 p66Shc mutant, and it was abolished in p66Shc−/− mouse splenocytes. Accordingly, the angiogenic response induced by the supernatants from hypoxic p66Shc−/− splenocytes was reduced dramatically when compared with the wild-type controls. In conclusion, hypoxic T cells may contribute to the onset of angiogenesis through a novel VEGF-mediated mechanism, where p66Shc acts as a positive regulator.

【 授权许可】

Unknown