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Inhibition of the Lipoxin A4 and Resolvin D1 Receptor Impairs Host Response to Acute Lung Injury Caused by Pneumococcal Pneumonia in Mice

Resolution of the acute respiratory distress syndrome (ARDS) from pneumonia requires repair of the injured lung endothelium and alveolar epithelium, removal of neutrophils from the distal airspaces of the lung, and clearance of the pathogen. Previous studies have demonstrated the importance of speci...

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Published in:American journal of physiology. Lung cellular and molecular physiology 2021-06, Vol.320 (6), p.L1085-L1092
Main Authors: Siegel, Emily R, Croze, Roxanne H, Fang, Xiaohui, Matthay, Michael A, Gotts, Jeffrey Earl
Format: Article
Language:English
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Summary:Resolution of the acute respiratory distress syndrome (ARDS) from pneumonia requires repair of the injured lung endothelium and alveolar epithelium, removal of neutrophils from the distal airspaces of the lung, and clearance of the pathogen. Previous studies have demonstrated the importance of specialized pro-resolving mediators (SPMs) in the regulation of host responses during inflammation. Although ARDS is commonly caused by Streptococcus pneumoniae, the role of Lipoxin A4 (LXA4) and Resolvin D1 (RvD1) in pneumococcal pneumonia is not well understood. In the present experimental study, we tested the hypothesis that endogenous SPMs play a role in the resolution of lung injury in a clinically relevant model of bacterial pneumonia. Blockade of ALX/FPR2, the receptor for LXA4 and RvD1, with the peptide WRW4 resulted in more pulmonary edema, greater protein accumulation in the air spaces, and increased bacteria accumulation in the air spaces and the blood. Inhibition of this receptor was also associated with decreased levels of pro-inflammatory cytokines. Even in the presence of antibiotic treatment, WRW4 inhibited the resolution of lung injury. In summary, these experiments demonstrated two novel findings: LXA4 and RvD1 contribute to the resolution of lung injury due to pneumococcal pneumonia, and the mechanism of their benefit likely includes augmenting bacterial clearance and reducing pulmonary edema via the restoration of lung alveolar-capillary barrier permeability.
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00046.2021