Depletion of circulating monocytes suppresses IL-17 and HMGB1 expression in mice with LPS-induced acute lung injury

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 macroph...

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Veröffentlicht in:American journal of physiology. Lung cellular and molecular physiology 2017-02, Vol.312 (2), p.L231-L242
Hauptverfasser: Jiang, Zhilong, Zhou, Qianlin, Gu, Chenlin, Li, Dandan, Zhu, Lei
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Sprache:eng
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Zusammenfassung: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.
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00389.2016