Abstract
The uncontrolled inflammatory response caused by a disorder in inflammation resolution is one of the reasons for acute respiratory distress syndrome (ARDS). The macrophage pool markedly expands when inflammatory monocytes, known as recruited macrophages, migrate from the circulation to the lung. The persistent presence of recruited macrophages leads to chronic inflammation in the resolution phase of inflammation. On the contrary, elimination of the recruited macrophages at the injury site leads to the rapid resolution of inflammation. Resolvin D1 (RvD1) is an endogenous lipid mediator derived from docosahexaenoic acid. Mice were administered RvD1 via the tail vein 3 and 4 days after stimulation with lipopolysaccharide. RvD1 reduced the levels of the inflammatory factors in the lung tissue, promoted the anti-inflammatory M2 phenotype, and enhanced the phagocytic function of recruited macrophages to alleviate acute lung injury. We also found that the number of macrophages was decreased in BAL fluid after treatment with RvD1. RvD1 increased the apoptosis of recruited macrophages partly via the FasL-FasR/caspase-3 signaling pathway, and this effect could be blocked by Boc-2, an ALX/PRP2 inhibitor. Taken together, our findings reinforce the concept of therapeutic targeting leading to the apoptosis of recruited macrophages. Thus, RvD1 may provide a new therapy for the resolution of ARDS.
Highlights
Acute respiratory distress syndrome (ARDS) is a common critical condition that results in high mortality [1]
We found that neutrophils in the alveolar lavage fluid markedly increased in the first three days, subsequently decreased slowly, and entered the phase of inflammation resolution
We found that treatment with Resolvin D1 (RvD1) during the peak of inflammation restored the body weights of the mice, improved the pathophysiological changes in their lungs, decreased TNF-α, IL-1β, and IL-6 levels in the lung tissue homogenate, and reduced neutrophil counts in the bronchoalveolar lavage fluid (BALF)
Summary
Acute respiratory distress syndrome (ARDS) is a common critical condition that results in high mortality [1]. Several molecules that play a role in alleviating inflammation have been elucidated and named as special anti-inflammatory mediators (SPM). These molecules exert anti-inflammatory and anti-infective effects [6]. Monocyte chemotactic protein (MCP)-1 promotes the recruitment of monocytes to inflammatory tissues to perform their functions [14] These two cell types play different functions in acute lung injury. Studies show that the depletion and recruitment of macrophages can reduce acute allergic lung inflammation [15]. We found that RvD1 administered at the peak of inflammation enhanced efferocytosis and M2 phenotype in the recruited macrophages and reduced the production of inflammatory cytokines.
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