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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4149-4158.
Prepublished online as a Blood First Edition Paper on February 2, 2006; DOI 10.1182/blood-2005-09-3808.
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PHAGOCYTES
CD44 is a phagocytic receptor
Eric Vachon,
Raiza Martin,
Jonathan Plumb,
Vivian Kwok,
R. William Vandivier,
Michael Glogauer,
Andras Kapus,
Xiaomin Wang,
Chung-Wai Chow,
Sergio Grinstein, and
Gregory P. Downey
From the Division of Respirology, Department of Medicine, University of Toronto, Toronto, ON, Canada; the Toronto General Hospital Research Institute of the University Health Network, Toronto, ON, Canada; the Research Institute of the Hospital for Sick Children, Toronto, ON, Canada; the Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Colorado, Denver, CO; and the Canadian Institutes of Health Research (CIHR) Group in Matrix Dynamics, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.
CD44, a transmembrane adhesion molecule involved in binding and metabolism of hyaluronan, has additional functions in inflammatory and immune responses, contributing to the ingestion and clearance of particles and apoptotic cells. Our goal was to determine the specific role of CD44 in phagocytosis and whether it functions as a primary or accessory phagocytic receptor. Using hyaluronan-coated beads and erythrocytes coated with antiCD44 antibodies as the phagocytic prey, we determined that CD44 mediates efficient phagocytosis in primary murine peritoneal macrophages and in the murine macrophage cell line RAW 264.7. In RAW cells, the phagocytic index for anti–CD44-coated erythrocytes was 25 ± 3 (mean ± SEM) compared with less than 1 for erythrocytes coated with isotype-matched control antibodies. Uptake of anti–CD44-coated erythrocytes was abrogated by pretreatment with a blocking antibody to CD44 and was absent in primary cultures of CD44-deficient murine macrophages. Down-regulation of Fc receptors by aggregated IgG-induced internalization, which blocks uptake of IgG-coated particles, had no effect on CD44-mediated particle engulfment. Using a combination of immunoprecipitation, pharmacologic inhibition, and genetic deletion, we determined that CD44-mediated phagocytosis involves Syk, Rac1, and phosphatidylinositol 3-kinase and induced activation of the phagocyte oxidase. We conclude that CD44 is a competent phagocytic receptor that efficiently mediates internalization of large particles.
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