Gene targeted inactivation of galectin-3 results in mice with reduced macrophage survival in culture

The β-galactoside-binding animal lectin, galectin-3, is widely expressed in various animal tissues and has been implicated in various physiological and pathological processes, including tumor transformation, RNA processing and inflammation. Previous studies have also suggested a role for galectin-3 in the regulation of cell growth and apoptosis. To definitively establish the function(s) of galectin-3. we have generated galectin-3 deficient (gal-3^-/-) mice by inactivation of the galectin-3 gene through homologous recombination. These mice do not have overt phenotypic abnormalities and are fertile. A role for galectin-3 in controlling apoptosis was studied by using inflammatory peritoneal macrophages which are known to normally express abundant amounts of galectin-3. We found that survival of macrophages from gal-3~/~ mice were markedly reduced compared to those from wild type mice following exposure to 7-interferon and lipopolysaccharide (LPS) in culture. Morphological changes of macrophages confirmed that these cells from gal- 3~/~ mice exhibit higher apoptotic tendencies following activation. A higher apoptotic index in macrophages from gal-3^-/- mice is further supported by results using in situ DNA nick end labeling. These results suggest that a major function of galeciin-3 in macrophages is suppression of apoptosis, and that this lectin may have an important role in regulating immune function and inflammation.