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 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-kappaB 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.
Hsu
D K
DK
Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Yang
R Y
RY
Pan
Z
Z
Yu
L
L
Salomon
D R
DR
Fung-Leung
W P
WP
Liu
F T
FT
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects; D015139:Blotting, Southern; D002448:Cell Adhesion; D002452:Cell Count; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D037502:Galectin 3; D018390:Gene Targeting / Q000379:methods; D006720:Homozygote; D037102:Lectins / Q000235:genetics*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics*; D016133:Polymerase Chain Reaction; D013864:Thioglycolates / Q000494:pharmacology
D000943:Antigens, Differentiation; D037502:Galectin 3; D037102:Lectins; D016328:NF-kappa B; D013864:Thioglycolates; D004247:DNA