CD44 is a phagocytic receptor.
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.
Vachon
Eric
E
Division of Respirology, Rm 6264 Medical Sciences Bldg, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
Martin
Raiza
R
Plumb
Jonathan
J
Kwok
Vivian
V
Vandivier
R William
RW
Glogauer
Michael
M
Kapus
Andras
A
Wang
Xiaomin
X
Chow
Chung-Wai
CW
Grinstein
Sergio
S
Downey
Gregory P
GP
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000235:genetics / Q000502:physiology*; D007109:Immunity; D007249:Inflammation / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D010587:Phagocytosis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000072377:Syk Kinase; D014162:Transfection
D018960:Hyaluronan Receptors; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse