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C-type natriuretic peptide attenuates lipopolysaccharide-induced acute lung injury in mice.

The Journal of surgical research (2014-12-09)
Toru Kimura, Takashi Nojiri, Hiroshi Hosoda, Shin Ishikane, Yasushi Shintani, Masayoshi Inoue, Mikiya Miyazato, Meinoshin Okumura, Kenji Kangawa
ABSTRACT

C-type natriuretic peptide (CNP), secreted by vascular endothelial cells, belongs to a family of peptides that includes atrial and brain natriuretic peptides. CNP exhibits many vasoprotective effects against pulmonary hypertension and pulmonary fibrosis. The objective of this study was to investigate the prophylactic effects of CNP in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). C57BL/6 mice were divided into three groups as follows: normal control mice (n = 13), LPS mice treated with vehicle (n = 12), and LPS mice treated with CNP (n = 12). Twenty-four hours after tail vein injection of LPS, histopathologic, gene expression, and bronchoalveolar lavage fluid (BALF) assessments were performed on the lungs. To examine the neutrophils in the lungs, cells positive for myeloperoxidase staining were detected by immunohistochemistry. BALF cytokine levels were analyzed by enzyme-linked immunosorbent assays. Gene expression in lung tissue was analyzed by real-time polymerase chain reaction. CNP significantly attenuated the elevation of leukocyte cell counts and levels of tumor necrosis factor-alpha, macrophage inflammatory protein-2, monocyte chemoattractant protein-1, interleukin-6, and keratinocyte-derived chemokine in the BALF after LPS injection. Furthermore, there were significantly fewer myeloperoxidase-positive cells in lungs treated with CNP after LPS injection. In lungs of CNP-treated mice, expression of the monocyte chemoattractant protein-1, S100A8, and E-selectin genes was significantly lower than that in vehicle-treated mice. CNP had a protective effect on ALI induced by LPS by reducing inflammatory cell infiltration. CNP may hold promise in therapeutic strategies for ALI after pulmonary resection surgery.

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