Hematopoietic Progenitor Cell Rolling in Bone Marrow Microvessels: Parallel Contributions by Endothelial Selectins and Vascular Cell Adhesion Molecule 1 |
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Authors: | Irina B. Mazo Jose-Carlos Gutierrez-Ramos Paul S. Frenette Richard O. Hynes Denisa D. Wagner Ulrich H. von Andrian |
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Affiliation: | From *The Center for Blood Research, the ‡Department of Pathology, and the §Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115; ‖Millenium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139; and the ¶Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 |
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Abstract: | We have used intravital microscopy to study physiologically perfused microvessels in murine bone marrow (BM). BM sinusoids and venules, but not adjacent bone vessels, supported rolling interactions of hematopoietic progenitor cells. Rolling did not involve L-selectin, but was partially reduced in wild-type mice treated with antibodies to P- or E-selectin and in mice that were deficient in these two selectins. Selectin-independent rolling was mediated by α4 integrins, which interacted with endothelial vascular cell adhesion molecule (VCAM)-1. Parallel contribution of the endothelial selectins and VCAM-1 is not known to direct blood cell trafficking to other noninflamed tissues. This combination of constitutively expressed adhesion molecules may thus constitute a BM-specific recruitment pathway for progenitor cells analogous to the vascular addressins that direct selective lymphocyte homing to lymphoid organs. |
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Keywords: | bone marrow, selectins, α 4 integrin, intravital microscopy, homing |
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