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• W2140656438 startingPage "1264" @default.
• W2140656438 abstract "Lung vascular permeability is acutely increased by high-pressure and high-volume ventilation. To determine the roles of mechanically activated cytosolic PLA 2 (cPLA 2 ) and Clara cell secretory protein (CCSP), a modulator of cPLA 2 activity, we compared lung injury with and without a PLA 2 inhibitor in wild-type mice and CCSP-null mice (CCSP −/− ) ventilated with high and low peak inflation pressures (PIP) for 2- or 4-h periods. After ventilation with high PIP, we observed significant increases in the bronchoalveolar lavage albumin concentrations, lung wet-to-dry weight ratios, and lung myeloperoxidase in both genotypes compared with unventilated controls and low-PIP ventilated mice. All injury variables except myeloperoxidase were significantly greater in the CCSP −/− mice relative to wild-type mice. Inhibition of cPLA 2 in wild-type and CCSP −/− mice ventilated at high PIP for 4 h significantly reduced bronchoalveolar lavage albumin and total protein and lung wet-to-dry weight ratios compared with vehicle-treated mice of the same genotype. Membrane phospho-cPLA 2 and cPLA 2 activities were significantly elevated in lung homogenates of high-PIP ventilated mice of both genotypes but were significantly higher in the CCSP −/− mice relative to the wild-type mice. Inhibition of cPLA 2 significantly attenuated both the phospho-cPLA 2 increase and increased cPLA 2 activity due to high-PIP ventilation. We propose that mechanical activation of the cPLA 2 pathway contributes to acute high PIP-induced lung injury and that CCSP may reduce this injury through inhibition of the cPLA 2 pathway and reduction of proinflammatory products produced by this pathway." @default.
• W2140656438 created "2016-06-24" @default.
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• W2140656438 date "2005-04-01" @default.
• W2140656438 modified "2023-10-18" @default.
• W2140656438 title "Clara cell secretory protein and phospholipase A₂activity modulate acute ventilator-induced lung injury in mice" @default.
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• W2140656438 doi "https://doi.org/10.1152/japplphysiol.01150.2004" @default.
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