Mannose Receptor In Lipopolysaccharide-induced Acute Lung Injury

Background:The mannose receptor(MR),a pattern recognizing innate receptor expressed on subsets of macrophages,immature dendritic cells and a population of endothelial cells is a key molecule in antigen recognition.Acute lung injury(ALI) is characterized by an acute inflammatory process in the airspaces and lung parenchyma,and lipopolysaccharide(LPS) has been recognized as a principal component causing it.In a study on chronic sinus diseases,quantitative real-time RT-PCR revealed statistically significant increased MMR mRNA expression in nasal polyps compared to chronic rhinosinusitis.Marzolo MP also revealed that mannose receptor is present in a functional state in rat microglial cells.But the relationship between mannose receptor and acute lung injury is not yet reported.Objective:We examined the mannose receptor in lipopolysaccharide-induced acute lung injury in mice,to evaluate its possible role in the onset and maintenance of acute lung injury.Materials and methods:Intratracheal administration of LPS induced acute lung injury.Three groups of Sprague-Dawley mice were used:1) the control group received an intratracheal instillation of saline,2) the LPS group received an intratracheal instillation of LPS(3 mg/kg),3) the dexamethasone(DXM) group was injected with DXM(0.5 mg/kg).In DXM group,drugs were administered by intravenous injection in the tail vein 5 min before and 3 h after intratracheal instillation of LPS.Lung wet/dry weight ratio, permeability index(PPI),total leukocytes and polymorphonuclear neutrophils(PMNs) counts in bronchoalveolar lavage fluid(BALF),myeloperoxidase(MPO) and monocyte chemotactic protein 1(MCP-1),tumor necrosis factor(TNF)-αand interleukin(IL)-1 in lung and BALF were determined.All the samples were investigated with real-time RT-PCR for quantification of mannose receptor mRNA expression,and Western Blot is used to test the amount of protein of nuclear transcription factor-κB(NF-κB) in the lung.Results:1.Mannose receptor is down-regulated in LPS-induced acute lung injury.Quantification of mannose receptor mRNA showed a statistically significant lower expression in LPS-induced acute lung injury compared to control group.The amount of mannose receptor mRNA decreased about 20.1%in the LPS group compared to control group(p＜0.05).2.DXM inhibited LPS-induced acute lung injury inflammation and up-regulated MR.Intratracheal instillation of LPS into the mice increased the lung wet/dry weight ratio from 4.07±0.31 to 4.67±0.37(P＜0.05).This LPS-induced pulmonary edema was significantly inhibited by DXM(0.5 mg/kg)(P＜0.05).MPO activity was increased by 58.8%in the lung tissue homogenate samples in the LPS group compared with the control group.LPS induced a dramatic increase in the concentration of TNF-αand IL-1b and MCP-1 in BAL fluid.Treatment with DXM attenuated this response. Quantification of mannose receptor mRNA showed a statistically significant higher expression in DXM group compared to LPS group.The amount of mannose receptor mRNA increased about 66.3%in the DXM group compared to LPS group(p＜0.05). 3.Increasing mannose receptor can inhibit the expression of NF-κB in LPS-induced acute lung injury.The nuclear NF-κB/p65 protein level in the LPS induced lung injury markedly increased to 4.5-fold greater when compared to the control.Pretreatment of mice with DXM(0.5mg/kg) significantly reduced the LPS induced expression of NF-κB/p65 in the lung.Mannose receptor significantly impaired the effect of DXM on reduction of NF-κB/p65 protein in the nuclei.Conclution:Mannose receptor is down-regulated in the LPS-induced acute lung injury.The nuclear NF-κB/p65 protein level in the LPS-induced acute lung injury markedly can be reduced by increasing the level of mannose receptor.The results of the present study indicate that mannose receptor plays an important role in the LPS-induced acute lung injury,it can inhibit TNF-αand IL-1βprotein and gene expression by blocking NF-κB activation.Mannose receptor appears to be a potential therapeutic target point for treating LPS-induced sepsis syndrome.