Targeted disruption of the galectin-3 gene results in attenuated peritoneal inflammatory responses

Galectin-3 is a member of a growing family of beta-galactoside-binding anim al lectins. Previous studies have demonstrated a variety of biological acti vities for this protein in vitro, including activation of cells, modulation of cell adhesion, induction of pre-mRNA splicing, and regulation of apopto sis. To assist in fully elucidating the physiological and pathological func tions of this protein, we have generated galectin-3-deficient (gal3(-/-)) m ice by targeted interruption of the galectin-3 gene. Gal3(-/-) mice consist ently developed fewer inflammatory cell infiltrations in the peritoneal cav ities than the wild-type (gal3(+/+)) mice in response to thioglycollate bro th treatment, mainly due to lower numbers of macrophages. Also, when compar ed to cells from gal5(+/+) mice, thioglycollate-elicited inflammatory cells from gal3(-/-) mice exhibited significantly lower levels of NF-kappa B res ponse. In addition, dramatically different cell-spreading phenotypes were o bserved in cultured macrophages from the two genotypes. Whereas macrophages from gal3(+/+) mice exhibited well spread out morphology, those from gal3( -/-) mice were often spindle-shaped, Finally, we found that peritoneal macr ophages from gal3(-/-) mite were more prone to undergo apoptosis than those from gal3(+/+) mice when treated with apoptotic stimuli, suggesting that e xpression of galectin-3 in inflammatory cells may lead to longer cell survi val, thus prolonging inflammation. These results strongly support galectin- 3 as a positive regulator of inflammatory responses in the peritoneal cavit y.