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Annexin A8 controls leukocyte recruitment to activated endothelial cells via cell surface delivery of CD63

Author

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  • Michaela Poeter

    (Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, and Interdisciplinary Clinical Research Center, University of Münster)

  • Ines Brandherm

    (Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, and Interdisciplinary Clinical Research Center, University of Münster)

  • Jan Rossaint

    (Intensive Care and Pain Medicine, University Hospital Münster
    Max-Planck Institute for Molecular Biomedicine)

  • Gonzalo Rosso

    (Institute of Physiology II, University of Münster)

  • Victor Shahin

    (Institute of Physiology II, University of Münster)

  • Boris V. Skryabin

    (Institute of Experimental Pathology, Center for Molecular Biology of Inflammation, and Interdisciplinary Clinical Research Center, University of Münster)

  • Alexander Zarbock

    (Intensive Care and Pain Medicine, University Hospital Münster
    Max-Planck Institute for Molecular Biomedicine)

  • Volker Gerke

    (Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, and Interdisciplinary Clinical Research Center, University of Münster)

  • Ursula Rescher

    (Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, and Interdisciplinary Clinical Research Center, University of Münster)

Abstract

To enable leukocyte adhesion to activated endothelium, the leukocyte receptor P-selectin is released from Weibel-Palade bodies (WPB) to the endothelial cell surface where it is stabilized by CD63. Here we report that loss of annexin A8 (anxA8) in human umbilical vein endothelial cells (HUVEC) strongly decreases cell surface presentation of CD63 and P-selectin, with a concomitant reduction in leukocyte rolling and adhesion. We confirm the compromised leukocyte adhesiveness in inflammatory-activated endothelial venules of anxA8-deficient mice. We find that WPB of anxA8-deficient HUVEC contain less CD63, and that this is caused by improper transport of CD63 from late multivesicular endosomes to WPB, with CD63 being retained in intraluminal vesicles. Consequently, reduced CD63 cell surface levels are seen following WPB exocytosis, resulting in enhanced P-selectin re-internalization. Our data support a model in which anxA8 affects leukocyte recruitment to activated endothelial cells by supplying WPB with sufficient amounts of the P-selectin regulator CD63.

Suggested Citation

  • Michaela Poeter & Ines Brandherm & Jan Rossaint & Gonzalo Rosso & Victor Shahin & Boris V. Skryabin & Alexander Zarbock & Volker Gerke & Ursula Rescher, 2014. "Annexin A8 controls leukocyte recruitment to activated endothelial cells via cell surface delivery of CD63," Nature Communications, Nature, vol. 5(1), pages 1-13, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4738
    DOI: 10.1038/ncomms4738
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