Toru Kimura1, Takashi Nojiri2, Hiroshi Hosoda3, Shin Ishikane4, Yasushi Shintani5, Masayoshi Inoue5, Mikiya Miyazato4, Meinoshin Okumura5, Kenji Kangawa4. 1. Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita-City, Osaka, Japan; Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan. Electronic address: kimura@thoracic.med.osaka-u.ac.jp. 2. Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita-City, Osaka, Japan; Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan. 3. Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, Suita-City, Osaka, Japan. 4. Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita-City, Osaka, Japan. 5. Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan.
Abstract
BACKGROUND: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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). MATERIALS AND METHODS: C57BL/6 mice were divided into three groups as follows: normal control mice (n = 13), LPSmice treated with vehicle (n = 12), and LPSmice 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. RESULTS: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. CONCLUSIONS: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.
Authors: Elizabeth O Harrington; Ashok Kumar; Verida Leandre; Zachary S Wilson; Brianna Guarino; Julie Braza; Craig T Lefort; James R Klinger Journal: Am J Physiol Lung Cell Mol Physiol Date: 2022-08-09 Impact factor: 6.011
Authors: Konstanze Michel; Melissa Herwig; Franziska Werner; Katarina Špiranec Spes; Marco Abeßer; Kai Schuh; Swati Dabral; Andreas Mügge; Hideo A Baba; Boris V Skryabin; Nazha Hamdani; Michaela Kuhn Journal: JCI Insight Date: 2020-11-19