Critical role of galectin-3 in phagocytosis by macrophages
Hideki Sano, … , Shozo Izui, Fu-Tong Liu
Hideki Sano, … , Shozo Izui, Fu-Tong Liu
Published August 1, 2003
Citation Information: J Clin Invest. 2003;112(3):389-397. https://doi.org/10.1172/JCI17592.
View: Text | PDF
Article Immunology

Critical role of galectin-3 in phagocytosis by macrophages

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.

Authors

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

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Impaired IgG-mediated phagocytosis of erythrocytes in gal3–/– mice in vi...
Impaired IgG-mediated phagocytosis of erythrocytes in gal3–/– mice in vivo. Experimental autoimmune hemolytic anemia was induced by an intraperitoneal injection of the anti–mouse rbc mAb 34-3C. (a) Three days after the injection, hematocrit was measured. The results are the mean ± SD from four mice of each genotype. (b) Liver sections of wild-type and gal3–/– mice were prepared and processed for H&E staining (original magnification, ×400). Open arrowheads point to Kupffer cells that do not contain rbc’s and filled arrowheads point to those with phagocytosed rbc’s. Arrows point to extramedullary hematopoietic foci. The inset shows a single Kupffer cell demonstrating erythrophagocytosis (original magnification, ×1,000).