Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 4843K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Shivtiel, S. Articles by Lapidot, T. PubMed PubMed Citation Articles by Shivtiel, S. Articles by Lapidot, T. Social Bookmarking                      What's this?

¹ Department of Immunology and ² Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel
³ The Laboratory of Musculoskeletal Biomechanics and Applied Anatomy, Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot 76100, Israel

CORRESPONDENCE Tsvee Lapidot: Tsvee.Lapidot{at}weizmann.ac.il

The CD45 phosphatase is uniquely expressed by all leukocytes, but its role in regulating hematopoietic progenitors is poorly understood. We show that enhanced CD45 expression on bone marrow (BM) leukocytes correlates with increased cell motility in response to stress signals. Moreover, immature CD45 knockout (KO) cells showed defective motility, including reduced homing (both steady state and in response to stromal-derived factor 1) and reduced granulocyte colony-stimulating factor mobilization. These defects were associated with increased cell adhesion mediated by reduced matrix metalloproteinase 9 secretion and imbalanced Src kinase activity. Poor mobilization of CD45KO progenitors by the receptor activator of nuclear factor B ligand, and impaired modulation of the endosteal components osteopontin and stem cell factor, suggested defective osteoclast function. Indeed, CD45KO osteoclasts exhibited impaired bone remodeling and abnormal morphology, which we attributed to defective cell fusion and Src function. This led to irregular distribution of metaphyseal bone trabecules, a region enriched with stem cell niches. Consequently, CD45KO mice had less primitive cells in the BM and increased numbers of these cells in the spleen, yet with reduced homing and repopulation potential. Uncoupling environmental and intrinsic defects in chimeric mice, we demonstrated that CD45 regulates progenitor movement and retention by influencing both the hematopoietic and nonhematopoietic compartments.

Abbreviations used: CFC, colony-forming cell; DC-STAMP, DC-specific transmembrane protein; Erk, extracellular signal-regulated kinase; FN, fibronectin; MMP, matrix metalloproteinase; MNC, mononuclear cell; PB, peripheral blood; PYD, pyridinoline; RANKL, receptor activator of NF-B ligand; SCF, stem cell factor; SDF-1, stromal-derived factor 1; SKL, Sca-1⁺/c-Kit⁺/Lin^–; Tb.N, trabecular number; TRAP, tartrate-resistant acid phosphatase; WBC, white blood cell.

© 2008 Shivtiel et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS