Abstract
The release of microparticles from eukaryotic cells is a well-recognized phenomenon. We demonstrate here that the chemokine receptor CCR5, the principal co-receptor for macrophage-tropic human immunodeficiency virus (HIV)-1, can be released through microparticles from the surface of CCR5+ Chinese hamster ovary cells and peripheral blood mononuclear cells. Microparticles containing CCR5 can transfer the receptor to CCR5− cells and render them CCR5+. The CCR5 transfer to CCR5-deficient peripheral blood mononuclear cells homozygous for a 32-base-pair deletion in the CCR5 gene enabled infection of these cells with macrophage-tropic HIV-1. In monocytes, the transfer of CCR5 could be inhibited by cytochalasin D, and transferred CCR5 could be downmodulated by chemokines. A transfer of CCR5 from peripheral blood mononuclear cells to endothelial cells during transendothelial migration could be demonstrated. Thus, the transfer of CCR5 may lead to infection of tissues without endogenous CCR5 expression. Moreover, the intercellular transfer of membrane proteins by microparticles might have broader consequences for intercellular communication beyond the effects seen for HIV-1.
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Acknowledgements
We thank M. Schellerer and T. Rupp for technical assistance. This work was supported by Deutsche Forschungsgemeinschaft grant MA2198/1-1 and Sonderforschungsbereich 464.
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Mack, M., Kleinschmidt, A., Brühl, H. et al. Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: A mechanism for cellular human immunodeficiency virus 1 infection . Nat Med 6, 769–775 (2000). https://doi.org/10.1038/77498
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DOI: https://doi.org/10.1038/77498
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