Inhibition of the lipoxin A4 and resolvin D1 receptor impairs host response to acute lung injury caused by pneumococcal pneumonia in mice

• DOI: 10.1152/ajplung.00046.2021
• Publication Date: 2021-04-06T17:05:26Z
• Authors: Emily R. Siegel; Roxanne H. Croze; Xiaohui Fang; Michael A. Matthay; Jeffrey E. Gotts
• Keywords: Pneumococcal pneumonia; Proinflammatory cytokine; Diffuse alveolar damage; Vascular permeability

Resolution of the acute respiratory distress syndrome (ARDS) from pneumonia requires repair injured lung endothelium and alveolar epithelium, removal neutrophils distal airspaces lung, clearance pathogen. Previous studies have demonstrated importance specialized proresolving mediators (SPMs) in regulation host responses during inflammation. Although ARDS is commonly caused by Streptococcus pneumoniae, role lipoxin A4 (LXA4) resolvin D1 (RvD1) pneumococcal not well understood. In present experimental study, we tested hypothesis that endogenous SPMs play a resolution injury clinically relevant model bacterial pneumonia. Blockade formyl peptide receptor 2 (ALX/FPR2), for LXA4 RvD1, with WRW4 resulted more pulmonary edema, greater protein accumulation air spaces, increased bacteria spaces blood. Inhibition this was also associated decreased levels proinflammatory cytokines. Even presence antibiotic treatment, inhibited injury. summary, these experiments two novel findings: RvD1 contribute to due pneumonia, mechanism their benefit likely includes augmenting reducing edema via restoration alveolar-capillary barrier permeability.