Comparative studies of mouse acute lung injury models induced by lipopolysaccharide and polyinosinic-polycytidylic acid

Abstract

Acute lung injury (ALI), its severe form, acute respiratory distress syndrome (ARDS), is a clinicalsyndrome characterized by acute hypoxic respiratory failure, bilateral lung infiltration with edema, andnormal cardiac filling pressure. There is no effective treatment for ALI/ARDS, and our understandingof its pathogenesis is partially based on animal models. With the widely use of Lipopolysaccharide (LPS)for bacterial infection-induced ALI, models for a viral infection-induced ALI are relatively rare. Thisstudy established ALI models using Polyinosinic-polycytidylic acid [poly(I:C)] and LPS intra-trachealinstallation, respectively, and systematic evaluations were conducted. Firstly, histological studiesby hematoxylin and eosin (HE) staining showed that poly(I:C) and LPS could induce inflammatorycell infiltration and structural changes. The lung injury was confirmed with the Wet/Dry ratio inboth treatments with a significantly higher ratio in poly(I:C) group. Total protein concentration inBronchoalveolar Lavage Fluid (BALF) from poly(I:C) and LPS treated groups were also significantlyincreased, while more protein concentration in LPS group than that in poly(I:C) group. Flow cytometryshowed that LPS promoted more alveolar neutrophil infiltration than poly(I:C). Secondly, quantitativePCR showed that poly(I:C) treatment promoted more expression of inflammatory factors, IL-1α, IL-6, TNF-α, and ICAM-1, with decreased expression of CCL-2. Finally, lung ventilation experimentsshowed that both poly(I:C) and LPS caused similar lung function loss with increased Newton resistancein poly(I:C) induced lung injury. In conclusion, poly(I:C) and LPS-induced ALIs were systematicallyevaluated, and distinct characteristics were associated with poly(I:C) induced lung injury. Our studiesmay provide the foundation for understanding the viral infection-induced ALI.