Critical role of galectin-3 in phagocytosis by macrophages.
Galectin-3 is a member of a large family of animal lectins. This protein is expressed abundantly by macrophages, but its function in this cell type is not well understood. We have studied the effect of galectin-3 gene targeting on phagocytosis, a major function of macrophages. Compared with wild-type macrophages, galectin-3-deficient (gal3-/-) cells exhibited reduced phagocytosis of IgG-opsonized erythrocytes and apoptotic thymocytes in vitro. In addition, gal3-/- mice showed attenuated phagocytic clearance of apoptotic thymocytes by peritoneal macrophages in vivo. These mice also exhibited reduced IgG-mediated phagocytosis of erythrocytes by Kupffer cells in a murine model of autoimmune hemolytic anemia. Additional experiments indicate that extracellular galectin-3 does not contribute appreciably to the phagocytosis-promoting function of this protein. Confocal microscopic analysis of macrophages containing phagocytosed erythrocytes revealed localization of galectin-3 in phagocytic cups and phagosomes. Furthermore, gal3-/- macrophages exhibited a lower degree of actin rearrangement upon Fcgamma receptor crosslinkage. These results indicate that galectin-3 contributes to macrophage phagocytosis through an intracellular mechanism. Thus, galectin-3 may play an important role in both innate and adaptive immunity by contributing to phagocytic clearance of microorganisms and apoptotic cells.
Sano
Hideki
H
Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California, USA.
Hsu
Daniel K
DK
Apgar
John R
JR
Yu
Lan
L
Sharma
Bhavya B
BB
Kuwabara
Ichiro
I
Izui
Shozo
S
Liu
Fu-Tong
FT
D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D004912:Erythrocytes / Q000276:immunology / Q000502:physiology; D037502:Galectin 3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007074:Immunoglobulin G / Q000378:metabolism; D066298:In Vitro Techniques; D007728:Kupffer Cells / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D017452:Receptors, IgG / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology
D037502:Galectin 3; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D017452:Receptors, IgG