title: Blockage of Galectin-receptor Interactions by α-lactose Exacerbates Plasmodium berghei-induced Pulmonary Immunopathology.
abstract: Malaria-associated acute lung injury (ALI) is a frequent complication of severe malaria that is often caused by "excessive" immune responses. To better understand the mechanism of ALI in malaria infection, here we investigated the roles of galectin (Gal)-1, 3, 8, 9 and the receptors of Gal-9 (Tim-3, CD44, CD137, and PDI) in malaria-induced ALI. We injected alpha (α)-lactose into mice-infected with Plasmodium berghei ANKA (PbANKA) to block galectins and found significantly elevated total proteins in bronchoalveolar lavage fluid, higher parasitemia and tissue parasite burden, and increased numbers of CD68(+) alveolar macrophages as well as apoptotic cells in the lungs after blockage. Additionally, mRNA levels of Gal-9, Tim-3, CD44, CD137, and PDI were significantly increased in the lungs at day 5 after infection, and the levels of CD137, IFN-α, IFN-β, IFN-γ, IL-4, and IL-10 in the lungs were also increased after α-lactose treatment. Similarly, the levels of Gal-9, Tim-3, IFN-α, IFN-β, IFN-γ, and IL-10 were all significantly increased in murine peritoneal macrophages co-cultured with PbANKA-infected red blood cells in vitro; but only IFN-α and IFN-β were significantly increased after α-lactose treatment. Our data indicate that Gal-9 interaction with its multiple receptors play an important role in murine malaria-associated ALI.
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong, China.|Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, Guangdong, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Medicine, Jinan University, Guangzhou 510632, Guangdong, China.
authors.forename: Shiguang
authors.initials: S
authors.lastname: Huang
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, United States of America.|State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
authors.forename: Xin-Zhuan
authors.initials: XZ
authors.lastname: Su
authors.affiliation: Institute of Science and Technology, Guangzhou University of Chinese Medicine, 436 Chentai Road, Baiyun District, Guangzhou 510445, Guangdong, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong, China.|Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, Guangdong, China.
authors.forename: Fangli
authors.initials: F
authors.lastname: Lu
mesh_terms: D053330:4-1BB Ligand / Q000276:immunology / Q000378:metabolism; D055371:Acute Lung Injury / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000469:parasitology; D005260:Female; D037161:Galectins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000276:immunology / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism; D007785:Lactose / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000469:parasitology; D008288:Malaria / Q000150:complications / Q000276:immunology* / Q000401:mortality; D051379:Mice; D010962:Plasmodium berghei / Q000472:pathogenicity*; D000097382:CD68 Molecule
chemical_list: D053330:4-1BB Ligand; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D037161:Galectins; D000072597:Hepatitis A Virus Cellular Receptor 2; D018960:Hyaluronan Receptors; D007785:Lactose; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C476399:Cd44 protein, mouse; C442241:Havcr2 protein, mouse; C505975:Tnfsf9 protein, mouse; C508186:galectin 9, mouse