The role of C5a and antibody in the release of heparan sulfate from endothelial cells

Authors

  • Jeffrey L. Platt,

    Corresponding author
    1. Department of Pediatrics, Immunobiology Research Center, University of Minnesota and the Veterans Administrative Medical Center, Minneapolis
    2. Department of Cell and Developmental Biology, Immunobiology Research Center, University of Minnesota and the Veterans Administrative Medical Center, Minneapolis
    • Immunobiology Research Center, University of Minnesota, Box 724 UMHC, Minneapolis, MN 55455, USA
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    • Established Investigator of the American Heart Association.

  • Agustin P. Dalmasso,

    1. Department of Pediatrics, Immunobiology Research Center, University of Minnesota and the Veterans Administrative Medical Center, Minneapolis
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    • Established Investigator of the American Heart Association.

  • Bonnie J. Lindman,

    1. Department of Cell and Developmental Biology, Immunobiology Research Center, University of Minnesota and the Veterans Administrative Medical Center, Minneapolis
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  • Nathan S. Ihrcke,

    1. Department of Pediatrics, Immunobiology Research Center, University of Minnesota and the Veterans Administrative Medical Center, Minneapolis
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  • Fritz H. Bach

    1. Department of Laboratory Medicine and Pathology, Immunobiology Research Center, University of Minnesota and the Veterans Administrative Medical Center, Minneapolis
    2. Department of Surgery, Immunobiology Research Center, University of Minnesota and the Veterans Administrative Medical Center, Minneapolis
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Abstract

The activation of endothelial cells is thought to contribute to the host response to infection and to the pathogenesis of autoimmune disease. It was recently shown that antibody and complement can activate endothelial cells leading to cleavage and release of heparan sulfate from the cells. We show here that release of heparan sulfate from endothelial cells is mediated by antibody and the complement fragment C5a and that assembly of the membrane attack complex and lysis of endothelial cells is not necessarily involved. These data suggest that the generation of C5a in conditions such as autoimmunity and infection in which anti-endothelial cell antibodies may also be present, might amplify tissue injury by a novel mechanism involving endothelial cell activation and loss of heparan sulfate mediated by antibody and C5a.

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