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Galectin-3 Is a Negative Regulator of Lipopolysaccharide-Mediated Inflammation¹

Yubin Li^*, Mousa Komai-Koma^*, Derek S. Gilchrist^*, Daniel K. Hsu, Fu-Tong Liu, Tabitha Springall^* and Damo Xu^2,*

^* Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, U.K.; and Department of Dermatology, School of Medicine, University of California-Davis, Sacramento, CA 95817

Galectin-3 is a β-galactoside-binding lectin that plays an important role in inflammatory diseases. It also interacts with the surface carbohydrates of many pathogens, including LPS. However, its role in infection is not fully understood. Data presented herein demonstrate for the first time that galectin-3 is a negative regulator of LPS-induced inflammation. Galectin-3 is constitutively produced by macrophages and directly binds to LPS. Galectin-3-deficient macrophages had markedly elevated LPS-induced signaling and inflammatory cytokine production compared with wild-type cells, which was specifically inhibited by the addition of recombinant galectin-3 protein. In contrast, blocking galectin-3 binding sites by using a neutralizing Ab or its ligand, β-lactose, enhanced LPS-induced inflammatory cytokine expression by wild-type macrophages. In vivo, mice lacking galectin-3 were more susceptible to LPS shock associated with excessive induction of inflammatory cytokines and NO production. However, these changes conferred greater resistance to Salmonella infection. Thus, galectin-3 is a previously unrecognized, naturally occurring, negative regulator of LPS function, which protects the host from endotoxin shock but, conversely, favors Salmonella survival.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study received financial support from the Medical Research Council U.K., the Wellcome Trust, and the Chief Scientist’s Office, Scotland.

² Address correspondence and reprint requests to Damo Xu, University of Glasgow, Glasgow Biomedical Research Centre, 120 University Place, Glasgow G12 8NT, U.K. E-mail address: d.xu{at}clinmed.gla.ac.uk

³ Abbreviations used in this paper: PAMP, pathogen-associated molecular pattern; BLP, bacterial lipopeptide; BMM, bone marrow-derived macrophage; CRD, carbohydrate recognition domain; PGN, peptidoglycan; ROS, reactive oxygen species; WT, wild type.