Nitric oxide synthase-2 down-regulates surfactant protein-B expression and enhances endotoxin-induced lung injury in mice

Autor: Mark A. Perrella, Irvith M. Carvajal, Larry A. Sonna, Edward P. Ingenito, George T. De Sanctis, Kathleen J. Haley, Laura E. Fredenburgh, Rebecca M. Baron, Yolanda Porrata, Michael L. Cullivan, Xiaoli Liu
Rok vydání: 2004
Předmět:
Lipopolysaccharides
Transcription
Genetic
Nitric Oxide Synthase Type II
Inflammation
Lung injury
Nitric Oxide
Biochemistry
Nitric oxide
chemistry.chemical_compound
Leukocyte Count
Mice
parasitic diseases
Genetics
medicine
Animals
Surface Tension
RNA
Messenger
Molecular Biology
Lung
Bone Marrow Transplantation
Aerosols
Mice
Knockout
Respiratory Distress Syndrome
Pulmonary Surfactant-Associated Protein B
biology
Pulmonary Surfactant-Associated Protein A
Interleukin-6
Tumor Necrosis Factor-alpha
Surfactant dysfunction
Nitric oxide synthase 2
respiratory system
Pulmonary Surfactant-Associated Protein C
Epithelium
Surfactant protein B
Cell biology
Specific Pathogen-Free Organisms
Mice
Inbred C57BL
medicine.anatomical_structure
chemistry
Radiation Chimera
Immunology
Models
Animal
biology.protein
medicine.symptom
Nitric Oxide Synthase
Bronchoalveolar Lavage Fluid
Biotechnology
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 18(11)
ISSN: 1530-6860
Popis: Acute respiratory distress syndrome (ARDS) is a life-threatening ailment characterized by severe lung injury involving inflammatory cell recruitment to the lung, cytokine production, surfactant dysfunction, and up-regulation of nitric oxide synthase 2 (NOS2) resulting in nitric oxide (NO) production. We hypothesized that NO production from NOS2 expressed in lung parenchymal cells in a murine model of ARDS would correlate with abnormal surfactant function and reduced surfactant protein-B (SP-B) expression. Pulmonary responses to nebulized endotoxin (lipopolysaccharide, LPS) were evaluated in wild-type (WT) mice, NOS2 null (-/-) mice, and NOS2-chimeric animals derived from bone marrow transplantation. NOS2-/- animals exhibited significantly less physiologic lung dysfunction and loss of SP-B expression than did WT animals. However, lung neutrophil recruitment and bronchoalveolar lavage cytokine levels did not significantly differ between NOS2-/- and WT animals. Chimeric animals for NOS2 exhibited the phenotype of the recipient and therefore demonstrated that parenchymal production of NOS2 is critical for the development of LPS-induced lung injury. Furthermore, administration of NO donors, independent of cytokine stimulation, decreased SP-B promoter activity and mRNA expression in mouse lung epithelial cells. This study demonstrates that expression of NOS2 in lung epithelial cells is critical for the development of lung injury and mediates surfactant dysfunction independent of NOS2 inflammatory cell expression and cytokine production.
Databáze: OpenAIRE
Externí odkaz: