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TRPV4 channels augment macrophage activation and ventilator-induced lung injury.

Publication ,  Journal Article
Hamanaka, K; Jian, M-Y; Townsley, MI; King, JA; Liedtke, W; Weber, DS; Eyal, FG; Clapp, MM; Parker, JC
Published in: Am J Physiol Lung Cell Mol Physiol
September 2010

We have previously implicated transient receptor potential vanilloid 4 (TRPV4) channels and alveolar macrophages in initiating the permeability increase in response to high peak inflation pressure (PIP) ventilation. Alveolar macrophages were harvested from TRPV4(-/-) and TRPV4(+/+) mice and instilled in the lungs of mice of the opposite genotype. Filtration coefficients (K(f)) measured in isolated perfused lungs after ventilation with successive 30-min periods of 9, 25, and 35 cmH(2)O PIP did not significantly increase in lungs from TRPV4(-/-) mice but increased >2.2-fold in TRPV4(+/+) lungs, TRPV4(+/+) lungs instilled with TRPV4(-/-) macrophages, and TRPV4(-/-) lungs instilled with TRPV4(+/+) macrophages after ventilation with 35 cmH(2)O PIP. Activation of TRPV4 with 4-alpha-phorbol didecanoate (4alphaPDD) significantly increased intracellular calcium, superoxide, and nitric oxide production in TRPV4(+/+) macrophages but not TRPV4(-/-) macrophages. Cross-sectional areas increased nearly 3-fold in TRPV4(+/+) macrophages compared with TRPV4(-/-) macrophages after 4alphaPDD. Immunohistochemistry staining of lung tissue for nitrotyrosine revealed increased amounts in high PIP ventilated TRPV4(+/+) lungs compared with low PIP ventilated TRPV4(+/+) or high PIP ventilated TRPV4(-/-) lungs. Thus TRPV4(+/+) macrophages restored susceptibility of TRPV4(-/-) lungs to mechanical injury. A TRPV4 agonist increased intracellular calcium and reactive oxygen and nitrogen species in harvested TRPV4(+/+) macrophages but not TRPV4(-/-) macrophages. K(f) increases correlated with tissue nitrotyrosine, a marker of peroxynitrite production.

Duke Scholars

Published In

Am J Physiol Lung Cell Mol Physiol

DOI

EISSN

1522-1504

Publication Date

September 2010

Volume

299

Issue

3

Start / End Page

L353 / L362

Location

United States

Related Subject Headings

  • Ventilator-Induced Lung Injury
  • Tyrosine
  • TRPC Cation Channels
  • Staining and Labeling
  • Respiratory System
  • Reactive Oxygen Species
  • Reactive Nitrogen Species
  • Pulmonary Ventilation
  • Pulmonary Edema
  • Phorbol Esters
 

Citation

APA
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ICMJE
MLA
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Hamanaka, K., Jian, M.-Y., Townsley, M. I., King, J. A., Liedtke, W., Weber, D. S., … Parker, J. C. (2010). TRPV4 channels augment macrophage activation and ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol, 299(3), L353–L362. https://doi.org/10.1152/ajplung.00315.2009
Hamanaka, Kazutoshi, Ming-Yuan Jian, Mary I. Townsley, Judy A. King, Wolfgang Liedtke, David S. Weber, Fabien G. Eyal, Mary M. Clapp, and James C. Parker. “TRPV4 channels augment macrophage activation and ventilator-induced lung injury.Am J Physiol Lung Cell Mol Physiol 299, no. 3 (September 2010): L353–62. https://doi.org/10.1152/ajplung.00315.2009.
Hamanaka K, Jian M-Y, Townsley MI, King JA, Liedtke W, Weber DS, et al. TRPV4 channels augment macrophage activation and ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2010 Sep;299(3):L353–62.
Hamanaka, Kazutoshi, et al. “TRPV4 channels augment macrophage activation and ventilator-induced lung injury.Am J Physiol Lung Cell Mol Physiol, vol. 299, no. 3, Sept. 2010, pp. L353–62. Pubmed, doi:10.1152/ajplung.00315.2009.
Hamanaka K, Jian M-Y, Townsley MI, King JA, Liedtke W, Weber DS, Eyal FG, Clapp MM, Parker JC. TRPV4 channels augment macrophage activation and ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2010 Sep;299(3):L353–L362.

Published In

Am J Physiol Lung Cell Mol Physiol

DOI

EISSN

1522-1504

Publication Date

September 2010

Volume

299

Issue

3

Start / End Page

L353 / L362

Location

United States

Related Subject Headings

  • Ventilator-Induced Lung Injury
  • Tyrosine
  • TRPC Cation Channels
  • Staining and Labeling
  • Respiratory System
  • Reactive Oxygen Species
  • Reactive Nitrogen Species
  • Pulmonary Ventilation
  • Pulmonary Edema
  • Phorbol Esters