RGD Reference Report - Clara cell secretory protein and phospholipase A2 activity modulate acute ventilator-induced lung injury in mice. - Rat Genome Database

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Clara cell secretory protein and phospholipase A2 activity modulate acute ventilator-induced lung injury in mice.

Authors: Yoshikawa, S  Miyahara, T  Reynolds, SD  Stripp, BR  Anghelescu, M  Eyal, FG  Parker, JC 
Citation: Yoshikawa S, etal., J Appl Physiol. 2005 Apr;98(4):1264-71. Epub 2004 Dec 17.
RGD ID: 5144143
Pubmed: PMID:15608088   (View Abstract at PubMed)
DOI: DOI:10.1152/japplphysiol.01150.2004   (Journal Full-text)

Lung vascular permeability is acutely increased by high-pressure and high-volume ventilation. To determine the roles of mechanically activated cytosolic PLA2 (cPLA2)and Clara cell secretory protein (CCSP), a modulator of cPLA2 activity, we compared lung injury with and without a PLA2 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 cPLA2 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-cPLA2 and cPLA2 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 cPLA2 significantly attenuated both the phospho-cPLA2 increase and increased cPLA2 activity due to high-PIP ventilation. We propose that mechanical activation of the cPLA2 pathway contributes to acute high PIP-induced lung injury and that CCSP may reduce this injury through inhibition of the cPLA2 pathway and reduction of proinflammatory products produced by this pathway.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Ventilator-Induced Lung Injury  ISOScgb1a1 (Mus musculus)5144143; 5144143 RGD 
Ventilator-Induced Lung Injury  IMP 5144143 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Scgb1a1  (secretoglobin family 1A member 1)

Genes (Mus musculus)
Scgb1a1  (secretoglobin, family 1A, member 1)

Genes (Homo sapiens)
SCGB1A1  (secretoglobin family 1A member 1)


Additional Information