Serum amyloid A3 confers protection against acute lung injury in<i>Pseudomonas aeruginosa</i>-infected mice

Abstract

<i>Pseudomonas aeruginosa</i> 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 <i>P. aeruginosa</i> is, therefore, of clinical importance. The present study identified serum amyloid A3 (SAA3) as being highly inducible in mouse bronchial epithelium following <i>P. aeruginosa</i> infection. Genetic deletion of <i>Saa3</i> rendered mice more susceptible to <i>P. aeruginosa</i> infection with decreased neutrophil superoxide anion production, and ex vivo treatment of mouse neutrophils with recombinant SAA3 restored the ability of neutrophils to produce superoxide anions. The SAA3-deficient mice showed exacerbated inflammatory responses, which was characterized by pronounced neutrophil infiltration, elevated expression of TNF-α, KC/CXCL1, and MIP-2/CXCL2 in bronchoalveolar lavage fluid (BALF), and increased lung microvascular permeability compared with their wild-type littermates. BALF neutrophils from <i>Saa3</i> knockout mice exhibited reduced superoxide anion production compared with neutrophils from wild-type mice. Adoptive transfer of SAA3-treated neutrophils to <i>Saa3</i> knockout mice ameliorated <i>P. aeruginosa</i>-induced acute lung injury. These findings demonstrate that SAA3 not only serves as a biomarker for infection and inflammation, but also plays a protective role against <i>P. aeruginosa</i> infection-induced lung injury in part through augmentation of neutrophil bactericidal functions.