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* Department of Pathology and Laboratory Medicine and
Jonsson Comprehensive Cancer Center, University of California Los Angeles School of Medicine, Los Angeles, CA 90095; and
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada
Disassembly and phagocytic removal of dying cells is critical to maintain immune homeostasis. The factors that regulate fragmentation and uptake of dying lymphocytes are not well understood. Degradation of fodrin, a cytoskeletal linker molecule that attaches CD45 to the actin cytoskeleton, has been described in apoptotic cells, although no specific initiator of fodrin degradation has been identified. CD45 is a glycoprotein receptor for galectin-1, an endogenous lectin that can trigger lymphocyte apoptosis, although CD45 is not required for phosphatidylserine externalization or DNA degradation during galectin-1 death. In this study, we show that fodrin degradation occurs during galectin-1 T cell death and that CD45 is essential for fodrin degradation to occur. In the absence of CD45, or if fodrin degradation is prevented, galectin-1-induced cell death is not accompanied by membrane blebbing, although phosphatidylserine externalization and DNA degradation proceed, indicating that fodrin degradation occurs via a distinct pathway compared with the pathway that leads to these other hallmarks of cell death. Moreover, there is slower phagocytic uptake by macrophages of T cells in which fodrin degradation is prevented, relative to T cells in which CD45-mediated fodrin degradation occurs. These studies identify a novel role for CD45 in regulating cellular disassembly and promoting phagocytic clearance during galectin-1-induced T cell death.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by National Institutes of Health Grant R01GM63281 (to L.G.B.) and National Institutes of Health Grants CA16042 and AI28697 (to the University of California Los Angeles Jonsson Comprehensive Cancer Center).
2 Current address: Profil Institute for Clinical Research, 855 3rd Avenue, Suite 4400, Chula Vista, CA 91911.
3 Address correspondence and reprint requests to Dr. Linda G. Baum, Department of Pathology and Laboratory Medicine, UCLA School of Medicine, 10833 LeConte Avenue, Los Angeles, CA 90095. E-mail address: lbaum{at}mednet.ucla.edu
4 Abbreviation used in this paper: RT, room temperature.
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