American journal of physiology. Lung cellular and molecular physiology | 2019
Serum amyloid A3 confers protection against acute lung injury in Pseudomonas aeruginosa-infected mice.
Abstract
Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative bacterium associated with serious illnesses including ventilator-associated pneumonia and various sepsis syndromes in humans. Understanding the host immune mechanisms against P. aeruginosa is therefore of clinical importance. The present study identified serum amyloid A3 (SAA3) as being highly inducible in mouse bronchial epithelium following P. aeruginosa infection. Genetic deletion of Saa3 rendered mice more susceptible to P. aeruginosa infection with exacerbated inflammatory response characterized by pronounced neutrophil infiltration, elevated expression of TNF-α, MIP-2 and KC in bronchoalveolar lavage fluid (BALF), and increased lung microvascular permeability compared with their WT littermates. BALF neutrophils from Saa3 knockout mice exhibited reduced superoxide production compared to neutrophils from wildtype mice. In vitro treatment of mouse neutrophils with SAA3 restored the abilities of the neutrophils to produce superoxide. Adoptive transfer of the treated neutrophils to Saa3 knockout mice ameliorated P. aeruginosa-induced acute lung injury. These findings demonstrate that local production of SAA3 not only serves as a biomarker for infection and inflammation but also plays a protective role against P. aeruginosa infection-induced lung injury partially through augmentation of neutrophil bactericidal functions.