title: Depletion of circulating monocytes suppresses IL-17 and HMGB1 expression in mice with LPS-induced acute lung injury.
abstract: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an important cause of mortality in critically ill patients. Macrophages play an important role in the pathogenesis of ALI/ARDS. To investigate the role and underlying mechanisms of circulating monocytes and resident alveolar macrophages (AMs) in ALI/ARDS, we depleted circulating monocytes and AMs by clodronate-loaded liposome (CL) in a lipopolysaccharide (LPS)-induced ALI/ARDS mouse model. Our results indicated that depletion of circulating monocytes by intravenous injection of CL 2 days before intratracheal LPS treatment significantly suppressed the acute lung injury in mice with ALI/ARDS, accompanied with significant reduction in neutrophil influx, interleukin-17, monocyte chemoattractant protein 1, high-mobility group box 1 protein, suppressor of cytokine signaling 3, and surfactant protein D (SP-D) in the lungs of 2 days intratracheal LPS-treated mice. In contrast, depletion of AMs by intratracheal delivery of CL enhanced the acute lung injury in association with upregulation of these mediators. Blocking monocyte chemoattractant protein 1 signaling by intraperitoneal instillation of anti-mouse CCL2 neutralizing antibody significantly reduced acute lung injury and neutrophil influx. In addition, SP-D was upregulated by mediators released from AMs because primary murine type II alveolar epithelial cells expressed more SP-D after treatment with bronchoalveolar lavage from LPS-treated mice or the conditioned media from LPS-treated RAW 264.7 cells. The results indicated that circulating monocytes are proinflammatory, but AMs have anti-inflammatory functions in the early phase of ALI/ARDS. The study provided a molecular basis for the treatment of ALI/ARDS through modulation of circulating monocytes and AMs.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China jiang.zhilong@zs-hospital.sh.cn.
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Qianlin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Chenlin
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000473:pathology; D056809:Alveolar Epithelial Cells / Q000378:metabolism; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D008070:Lipopolysaccharides; D008262:Macrophage Activation; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D015398:Signal Transduction; D058504:Th17 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018932:Chemokine CCL2; D018925:Chemokines; D024243:HMGB1 Protein; D020381:Interleukin-17; D008070:Lipopolysaccharides; D037663:Pulmonary Surfactant-Associated Protein D; D014409:Tumor Necrosis Factor-alpha
keywords: acute lung injury/acute respiratory distress syndrome; alveolar macrophage; circulating monocytes; high-mobility group box 1 protein; interleukin-17; lipopolysaccharide; surfactant protein D