ABSTRACT
The objective of this study was to characterize a mouse model of lung inflammation and determine the effect of surfactant protein A (SP-A, or sftpa) on the transfer of inflammatory mediators from these injured lungs into the systemic circulation. Lung inflammation was induced in either sftpa-deficient (-/-) or wild-type (+/+) spontaneously breathing, adult mice via intranasal lipopolysaccharide (LPS). Four hours later, lungs were isolated, perfused, and mechanically ventilated for 2 hours. Perfusate was collected for analysis over the duration of ventilation and lung lavage was obtained in groups of animals immediately before and after mechanical ventilation (MV). Lavage analysis showed an increase in interleukin-6 (IL6) and tumor necrosis factor-alpha (TNFalpha) 4 hours after LPS, with a further increase in IL6 following MV. LPS and MV also caused an increase in total cell and neutrophil numbers as well as total protein in the lavage compared to controls. Perfusate analysis revealed a significant increase in IL6 and TNFalpha after LPS and MV, with significantly greater levels of these mediators in sftpa (-/-) versus (+/+) mice. The authors conclude that LPS followed by MV resulted in lung inflammation and injury, and that SP-A significantly influenced inflammatory mediator release from these inflamed lungs into the perfusate.
Subject(s)
Inflammation Mediators/metabolism , Pneumonia/metabolism , Pulmonary Surfactant-Associated Protein A/physiology , Animals , Blood Circulation , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Disease Models, Animal , Inflammation Mediators/blood , Interleukin-6/blood , Interleukin-6/metabolism , Lipopolysaccharides/immunology , Lung/metabolism , Lung/physiopathology , Male , Mice , Mice, Knockout , Neutrophils/immunology , Pneumonia/physiopathology , Pulmonary Surfactant-Associated Protein A/genetics , Respiration, Artificial/adverse effects , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Tissue inhibitor of metalloproteinase-3 (TIMP3) null mice develop emphysema-like airspace enlargement due to an enzymatic imbalance. This study investigates how these abnormalities alter lung mechanics and the response to 2 different mechanical ventilation strategies. Phenotypically, TIMP3 null mice had increased compliance, and decreased resistance, tissue damping, and tissue elastance over wild-type controls. Decreased compliance and increased resistance were observed following the injurious ventilation strategy; however, the TIMP3 null response to both ventilation strategies was similar to wild-type mice. In conclusion, TIMP3 null mice have significant alterations in lung mechanics; however, this does not affect their response to ventilation.
