Post-burn lung inflammation is associated with induction of pulmonary cathelicidin-related antimicrobial peptide and S100a8 in mice.

Abstract

Burn trauma triggers dysregulated systemic inflammation, leading to multi-organ dysfunction. Respiratory failure often follows burn injury, resulting in morbidity and mortality, in part, because of excessive and prolonged release of local and systemic pro-inflammatory mediators. One class of important mediators of inflammation at mucosal surfaces are antimicrobial peptides (AMPs), and their expression is notably altered in inflammation. We sought to determine whether pulmonary AMPs are induced in inflammatory lung after burn. C57BL/6 male mice were given a 12-15% full thickness total body surface area dorsal scald burn or sham injury. Survival rate and pulmonary function of the mice were assessed at 24 hours. Histopathological examination and quantification of pro-inflammatory mediators, IL-6 and CXCL1, in the lungs at 24 hours after burn were performed. mRNA expression of a subset of prominent lung AMPs in whole lung, alveolar macrophages, and primary lung epithelial cells were measured. Our data showed decreased survival and impaired respiratory function after burn injury. Moreover, hematoxylin and eosin-stained lung sections of burned mice showed pulmonary edema and congestion, and pulmonary IL-6 and CXCL1 were elevated. AMP analysis revealed that burn triggered a dramatic rise in lung Camp and S100a8 above that of sham mice. To our surprise, lung epithelial cells, and not alveolar macrophages, were the cellular source of burn-induced Camp and S100a8 in this murine model of burn injury. Taken together, these data reveal for the first time that lung inflammation post-burn involves a rise in AMPs, Camp and S100a8, from lung epithelial cells.