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

Daniel K. Hsu, Ri Yao Yang, Zhixing Pan, Lan Yu, Daniel R. Salomon, Wai Ping Fung-Leung, Fu-Tong Liu

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345 Scopus citations

Abstract

Galectin-3 is a member of a growing family of β-galactoside-binding animal lectins. Previous studies have demonstrated a variety of biological activities for this protein in vitro, including activation of cells, modulation of cell adhesion, induction of pre-mRNA splicing, and regulation of apoptosis. To assist in fully elucidating the physiological and pathological functions of this protein, we have generated galectin-3-deficient (gal3(-/-)) mice by targeted interruption of the galectin-3 gene. Gal3(-/-) mice consistently developed fewer inflammatory cell infiltrations in the peritoneal cavities than the wild-type (gal3(+/+)) mice in response to thioglycollate broth treatment, mainly due to lower numbers of macrophages. Also, when compared to cells from gal3(+/+) mice, thioglycollate-elicited inflammatory cells from gal3(-/-) mice exhibited significantly lower levels of NF-κB response. In addition, dramatically different cell-spreading phenotypes were observed 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 macrophages from gal3(-/-) mice were more prone to undergo apoptosis than those from gal3(+/+) mice when treated with apoptotic stimuli, suggesting that expression of galectin-3 in inflammatory cells may lead to longer cell survival, thus prolonging inflammation. These results strongly support galectin-3 as a positive regulator of inflammatory responses in the peritoneal cavity.

Original languageEnglish (US)
Pages (from-to)1073-1083
Number of pages11
JournalAmerican Journal of Pathology
Volume156
Issue number3
StatePublished - 2000

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Hsu, D. K., Yang, R. Y., Pan, Z., Yu, L., Salomon, D. R., Fung-Leung, W. P., & Liu, F-T. (2000). Targeted disruption of the Galectin-3 gene results in attenuated peritoneal inflammatory responses. American Journal of Pathology, 156(3), 1073-1083.