Atrial natriuretic peptide protects against XXXX -induced lung injury and endothelial barrier dysfunction.

@entity14662 @entity1 @entity295 @entity55 @entity19 @entity794 @entity281 @entity26800 @entity647
@entity55 and alterations in endothelial cell (EC) permeability are key events to development of @entity647 ( @entity647 ). Protective effects of atrial natriuretic peptide (ANP) have been shown against inflammatory signaling and endothelial barrier dysfunction induced by gram-negative bacterial wall liposaccharide. We hypothesized that ANP may possess more general protective effects and @entity55 and EC barrier dysfunction by suppressing inflammatory cascades and barrier-disruptive mechanisms shared by gram-negative and gram-positive pathogens. C57BL/6J wild-type or ANP knockout @entity19 ( @entity14662 -/-) were treated with gram-positive bacterial cell wall compounds, @entity794 -derived peptidoglycan (PepG) and/or lipoteichoic acid ( @entity26800 ) (intratracheal, 2.5 mg/kg each), with or without ANP (intravenous, 2  g/kg). In vitro, @entity1 pulmonary EC barrier properties were assessed by morphological analysis of gap formation and measurements of transendothelial electrical resistance. LTA and PepG markedly increased pulmonary EC permeability and activated p38 and ERK1/2 MAP kinases, NF-kB, and Rho/Rho kinase signaling. EC barrier dysfunction was further elevated upon combined LTA and PepG treatment, but abolished by ANP pretreatment. In vivo, LTA and PepG-induced accumulation of protein and cells in the bronchoalveolar lavage fluid, tissue neutrophil infiltration, and increased Evans blue extravasation in the lungs was significantly attenuated by intravenous injection of ANP. Accumulation of bronchoalveolar lavage markers of LTA/PepG-induced @entity55 and barrier dysfunction was further augmented in ANP-/- @entity19 and attenuated by exogenous ANP injection. These results strongly suggest a protective role of ANP in the in vitro and in vivo models of @entity647 associated with gram-positive @entity281 . Thus ANP may have important implications in therapeutic strategies aimed at the treatment of @entity295 and @entity647 -induced gram-positive bacterial pathogens.
