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Critical role of galectin-3 in phagocytosis by macrophages

Sano, Hideki
Hsu, D. K.
Apgar, J. R.
Yu, Lan
Sharma, B. B.
Kuwabara, Ichiro
Liu, F. T.
Published in Journal of Clinical Investigation. 2003, vol. 112, no. 3, p. 389-397
Abstract 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.
Keywords Anemia, Hemolytic, Autoimmune/immunology/pathology/physiopathologyAnimalsApoptosisErythrocytes/immunology/physiologyGalectin 3/deficiency/genetics/ physiologyImmunoglobulin G/metabolismKupffer Cells/physiologyMacrophages, Peritoneal/ physiologyMiceMice, Inbred C57BLMice, KnockoutOpsonin Proteins/metabolismPhagocytosis/ physiologyReceptors, IgG/metabolismT-Lymphocytes/cytology/immunology/physiology
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PMID: 12897206
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