Critical role of galectin-3 in phagocytosis by macrophages

Hideki Sano, Daniel K. Hsu, John R. Apgar, Lan Yu, Bhavya B. Sharma, Ichiro Kuwabara, Shozo Izui, Fu-Tong Liu

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277 Scopus citations

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 Fcγ 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.

Original languageEnglish (US)
Pages (from-to)389-397
Number of pages9
JournalJournal of Clinical Investigation
Volume112
Issue number3
DOIs
StatePublished - Aug 2003

ASJC Scopus subject areas

  • Medicine(all)

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    Sano, H., Hsu, D. K., Apgar, J. R., Yu, L., Sharma, B. B., Kuwabara, I., Izui, S., & Liu, F-T. (2003). Critical role of galectin-3 in phagocytosis by macrophages. Journal of Clinical Investigation, 112(3), 389-397. https://doi.org/10.1172/JCI200317592