TY - JOUR
T1 - Mechanical ventilation enhances lung inflammation and caspase activity in a model of mouse pneumovirus infection
AU - Bem, Reinout Alexander
AU - van Woensel, Job B. M.
AU - Bos, Albert P.
AU - Koski, Amy
AU - Farnand, Alex W.
AU - Domachowske, Joseph B.
AU - Rosenberg, Helene F.
AU - Martin, Thomas R.
AU - Matute-Bello, Gustavo
PY - 2009
Y1 - 2009
N2 - Severe infection with respiratory syncytial virus (RSV) in children can progress to respiratory distress and acute lung injury (ALI). Accumulating evidence suggests that mechanical ventilation (MV) is an important cofactor in the development of ALI by modulating the host immune responses to bacteria. This study investigates whether MV enhances the host response to pneumonia virus of mice (PVM), a mouse pneumovirus that has been used as a model for RSV infection in humans. BALB/c mice were inoculated intranasally with diluted clarified lung homogenates from mice infected with PVM strain J3666 or uninfected controls. Four days after inoculation the mice were subjected to 4 hr of MV (Vt 10 ml/kg), or allowed to breathe spontaneously. As compared with mice inoculated with PVM-only, the administration of MV to PVM-infected mice resulted in increased bronchoalveolar lavage fluid (BALF) concentrations of the cytokines MIP-2, MIP-1alpha (CCL3) and IL-6; increased alveolar-capillary permeability to high molecular weight proteins; and increased caspase-3 activity in lung homogenates. We conclude that MV enhances the activation of inflammatory and caspase cell death pathways in response to pneumovirus infection. We speculate that MV potentially contributes to the development of lung injury in patients with RSV infection. Key words: RSV, Mechanical ventilation, Acute lung injury, Mouse
AB - Severe infection with respiratory syncytial virus (RSV) in children can progress to respiratory distress and acute lung injury (ALI). Accumulating evidence suggests that mechanical ventilation (MV) is an important cofactor in the development of ALI by modulating the host immune responses to bacteria. This study investigates whether MV enhances the host response to pneumonia virus of mice (PVM), a mouse pneumovirus that has been used as a model for RSV infection in humans. BALB/c mice were inoculated intranasally with diluted clarified lung homogenates from mice infected with PVM strain J3666 or uninfected controls. Four days after inoculation the mice were subjected to 4 hr of MV (Vt 10 ml/kg), or allowed to breathe spontaneously. As compared with mice inoculated with PVM-only, the administration of MV to PVM-infected mice resulted in increased bronchoalveolar lavage fluid (BALF) concentrations of the cytokines MIP-2, MIP-1alpha (CCL3) and IL-6; increased alveolar-capillary permeability to high molecular weight proteins; and increased caspase-3 activity in lung homogenates. We conclude that MV enhances the activation of inflammatory and caspase cell death pathways in response to pneumovirus infection. We speculate that MV potentially contributes to the development of lung injury in patients with RSV infection. Key words: RSV, Mechanical ventilation, Acute lung injury, Mouse
U2 - https://doi.org/10.1152/ajplung.00467.2007
DO - https://doi.org/10.1152/ajplung.00467.2007
M3 - Article
C2 - 18996903
SN - 1040-0605
VL - 296
SP - L46-L56
JO - American journal of physiology. Lung cellular and molecular physiology
JF - American journal of physiology. Lung cellular and molecular physiology
IS - 1
ER -