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Insulin Growth Factor-I Inhibits Apoptosis in Hematopoietic: Progenitor Cells Implications in Thymic Aginga

Authors

  • KEITH W. KELLEY,

    Corresponding author
    1. Laboratory of Immunophysiology, Department of Animal Sciences, University of Illinois, 1201 West Gregory Drive, Urbana, Illinois 61801 USA
      Address for correspondence: Dr. Keith W. Kelley, Laboratory of Immunophysiology, 207 Edward R. Madigan Laboratory, 1201 West Gregory Drive, University of Illinois, Urbana, IL 61801; Telephone: 217-333-5141; Fax: 217-244-5617; e-mail: kwkelley@uiuc.edu
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  • WILLIAM A. MEIER,

    1. Laboratory of Immunophysiology, Department of Animal Sciences, University of Illinois, 1201 West Gregory Drive, Urbana, Illinois 61801 USA
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  • CHRISTIAN MINSHALL,

    1. Laboratory of Immunophysiology, Department of Animal Sciences, University of Illinois, 1201 West Gregory Drive, Urbana, Illinois 61801 USA
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  • DANIEL H. SCHACHER,

    1. Laboratory of Immunophysiology, Department of Animal Sciences, University of Illinois, 1201 West Gregory Drive, Urbana, Illinois 61801 USA
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  • QIANG LIU,

    1. Laboratory of Immunophysiology, Department of Animal Sciences, University of Illinois, 1201 West Gregory Drive, Urbana, Illinois 61801 USA
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  • ROGER VANHOY,

    1. Laboratory of Immunophysiology, Department of Animal Sciences, University of Illinois, 1201 West Gregory Drive, Urbana, Illinois 61801 USA
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  • WILLIAM BURGESS,

    1. Laboratory of Immunophysiology, Department of Animal Sciences, University of Illinois, 1201 West Gregory Drive, Urbana, Illinois 61801 USA
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  • ROBERT DANTZER

    1. Laboratory of Integrative Neurobiology, INRA-INSERM, U934, Rue Camille-Saint-Saëns, 33077 Bordeaux, France
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  • a

    This work was supported by the National Institutes of Health AG-06246.

Address for correspondence: Dr. Keith W. Kelley, Laboratory of Immunophysiology, 207 Edward R. Madigan Laboratory, 1201 West Gregory Drive, University of Illinois, Urbana, IL 61801; Telephone: 217-333-5141; Fax: 217-244-5617; e-mail: kwkelley@uiuc.edu

Abstract

Abstract: A decline in plasma concentrations of both growth hormone and IGF-I occurs during aging of humans and rodents, and this is accompanied by involution of the thymus gland. Exogenous growth hormone induces the synthesis of IGF-I, which acts on bone marrow-derived hematopoietic progenitors of the myeloid and lymphoid lineages to promote their replication and survival. The increase in survival of these cells is caused by the ability of IGF-I to inhibit their apopotic death. In contrast to the multipotential colony-stimulating-factor IL-3, inhibition of apoptosis by IGF-I requires the activation of the critical intracellular effector PI 3-kinase. These data establish that hematopoietic progenitors can use more than one intracellular signaling pathway in order to maintain their survival. The data also extend the original hypothesis 48 that IGF-I shares with the colony-stimulating factors the properties of promoting DNA synthesis and inhibiting programmed cell death. Collectively, these data establish that hematopoietic progenitor cells are important targets for IGF-I, and this is likely to be important in understanding thymic aging.

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