title: Involvement of mannose receptor in the preventive effects of mannose in lipopolysaccharide-induced acute lung injury.
abstract: Although macrophage mannose receptor contributes to the anti-inflammatory procedure, its mechanisms of action are incompletely understood in acute lung injury. We recently found that mannose which could bind to mannose receptor, prevented acute lung injury in rats. Here, we profiled the involvement of mannose receptor in the preventive effects of mannose in lipopolysaccharide-induced acute lung injury in mice. We found that pulmonary edema, protein exudation, and lung histopathology were significantly improved in a dose-dependent manner among the mannose (50, 150, and 450 mg/kg) mice (a bolus tail vein injection of mannose 5 min before and 3h after intratracheal instillation of LPS) compared to the LPS mice. Mannose also prevented the inflammatory cell accumulation, and inhibited production of cytokines. Further, in the in vitro alveolar macrophages, treatment with mannose resulted in decreased phagocytic activity and production of cytokines, and its anti-inflammatory effects were associated with up-regulation of mannose receptor. Importantly, we found that competitive inhibition of mannose receptor (mannan 2mg/ml) or targeted short interfering RNA-mediated gene suppression of mannose receptor mRNA was associated with the elimination of the anti-inflammatory effects of mannose. Furthermore, the up-regulation of mannose receptor by mannose administration was associated with inhibited NF-kappaB nuclear translocation. Taken together, these studies reveal involvement of mannose receptor and impaired NF-kappaB activation in the mannose prevention of acute lung injury, and implicate mannose receptor as a potential therapeutic target during acute lung injury.
authors.affiliation: Department of Respiratory Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xuanli
authors.initials: X
authors.lastname: Xu
authors.forename: Qiangmin
authors.initials: Q
authors.lastname: Xie
authors.forename: Yihong
authors.initials: Y
authors.lastname: Shen
authors.forename: Guohua
authors.initials: G
authors.lastname: Lu
authors.forename: Hongyi
authors.initials: H
authors.lastname: Yao
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhou
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000517:prevention & control; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000009:adverse effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins; D037181:Lectins, C-Type / Q000378:metabolism* / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008358:Mannose / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011897:Random Allocation; D011956:Receptors, Cell Surface / Q000378:metabolism* / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D004731:Endotoxins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C044101:endotoxin, Escherichia coli; D008358:Mannose