This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200305-660OCv1 169/4/518    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, L.-F. Articles by Quinn, D. A. Search for Related Content PubMed PubMed Citation Articles by Li, L.-F. Articles by Quinn, D. A.

Ventilation-induced Neutrophil Infiltration Depends on c-Jun N-Terminal Kinase

Pulmonary and Critical Care Units, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan, Republic of China

Correspondence and requests for reprints should be addressed to Deborah A. Quinn, M.D., Pulmonary and Critical Care Unit, Massachusetts General Hospital, 55 Fruit Street, Bulfinch 148, Boston, MA 02114. E-mail: dquinn1{at}partners.org

Positive pressure ventilation with large VTs has been shown to cause release of cytokines, including macrophage inflammatory protein-2 (MIP-2), a functional equivalent of human interleukin-8. The mechanisms regulating ventilation-induced cytokine production are unclear. Based on our previous in vitro model of lung cell stretch, we hypothesized that high VT ventilation–induced MIP-2 production is dependent on the activation of the c-Jun N-terminal kinase (JNK). We exposed C57BL/6 mice to high VT (30 ml/kg) or low VT (6 ml/kg) mechanical ventilation for 5 hours. High VT ventilation–induced neutrophil migration into the lung, MIP-2 protein production, MIP-2 messenger RNA expression, and JNK activation. Large VT ventilation of JNK knockout mice and pharmacologic JNK inhibition with SP600125 attenuated neutrophil sequestration and blocked MIP-2 messenger RNA expression and MIP-2 production. We conclude that lung cell stretch in vivo results in increased lung neutrophil sequestration and increased MIP-2 production, which was, at least in part, dependent upon the JNK pathway.

Key Words: chemokine • mitogen-activated protein kinase • lung stretch

This article has been cited by other articles:

				C. Wray, Y. Mao, J. Pan, A. Chandrasena, F. Piasta, and J. A. Frank Claudin-4 augments alveolar epithelial barrier function and is induced in acute lung injury Am J Physiol Lung Cell Mol Physiol, August 1, 2009; 297(2): L219 - L227. [Abstract] [Full Text] [PDF]

				M. Mongan, Z. Tan, L. Chen, Z. Peng, M. Dietsch, B. Su, G. Leikauf, and Y. Xia Mitogen-activated Protein Kinase Kinase Kinase 1 Protects against Nickel-induced Acute Lung Injury Toxicol. Sci., August 1, 2008; 104(2): 405 - 411. [Abstract] [Full Text] [PDF]

				C. D. Ochoa, H. Baker, S. Hasak, R. Matyal, A. Salam, C. A. Hales, W. Hancock, and D. A. Quinn Cyclic Stretch Affects Pulmonary Endothelial Cell Control of Pulmonary Smooth Muscle Cell Growth Am. J. Respir. Cell Mol. Biol., July 1, 2008; 39(1): 105 - 112. [Abstract] [Full Text] [PDF]

				S. Papaiahgari, A. Yerrapureddy, S. R. Reddy, N. M. Reddy, J. M. Dodd-O, M. T. Crow, D. N. Grigoryev, K. Barnes, R. M. Tuder, M. Yamamoto, et al. Genetic and Pharmacologic Evidence Links Oxidative Stress to Ventilator-induced Lung Injury in Mice Am. J. Respir. Crit. Care Med., December 15, 2007; 176(12): 1222 - 1235. [Abstract] [Full Text] [PDF]

				T. Miyahara, K. Hamanaka, D. S. Weber, D. A. Drake, M. Anghelescu, and J. C. Parker Phosphoinositide 3-kinase, Src, and Akt modulate acute ventilation-induced vascular permeability increases in mouse lungs Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L11 - L21. [Abstract] [Full Text] [PDF]

				H.-Y. Cho, D. L. Morgan, A. K. Bauer, and S. R. Kleeberger Signal Transduction Pathways of Tumor Necrosis Factor-mediated Lung Injury Induced by Ozone in Mice Am. J. Respir. Crit. Care Med., April 15, 2007; 175(8): 829 - 839. [Abstract] [Full Text] [PDF]

				R.-E. E. Abdulnour, X. Peng, J. H. Finigan, E. J. Han, E. J. Hasan, K. G. Birukov, S. P. Reddy, J. E. Watkins III, U. S. Kayyali, J. G. N. Garcia, et al. Mechanical stress activates xanthine oxidoreductase through MAP kinase-dependent pathways Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L345 - L353. [Abstract] [Full Text] [PDF]

				B. Han, M. Lodyga, and M. Liu Ventilator-induced Lung Injury: Role of Protein-Protein Interaction in Mechanosensation Proceedings of the ATS, October 1, 2005; 2(3): 181 - 187. [Abstract] [Full Text] [PDF]

				P. G. Arndt, S. K. Young, and G. S. Worthen Regulation of Lipopolysaccharide-Induced Lung Inflammation by Plasminogen Activator Inhibitor-1 through a JNK-Mediated Pathway J. Immunol., September 15, 2005; 175(6): 4049 - 4059. [Abstract] [Full Text] [PDF]

				W. A. Altemeier, G. Matute-Bello, S. A. Gharib, R. W. Glenny, T. R. Martin, and W. C. Liles Modulation of Lipopolysaccharide-Induced Gene Transcription and Promotion of Lung Injury by Mechanical Ventilation J. Immunol., September 1, 2005; 175(5): 3369 - 3376. [Abstract] [Full Text] [PDF]

				X. Peng, R.-E. E. Abdulnour, S. Sammani, S.-F. Ma, E. J. Han, E. J. Hasan, R. Tuder, J. G. N. Garcia, and P. M. Hassoun Inducible Nitric Oxide Synthase Contributes to Ventilator-induced Lung Injury Am. J. Respir. Crit. Care Med., August 15, 2005; 172(4): 470 - 479. [Abstract] [Full Text] [PDF]

				P. Caironi, F. Ichinose, R. Liu, R. C. Jones, K. D. Bloch, and W. M. Zapol 5-Lipoxygenase Deficiency Prevents Respiratory Failure during Ventilator-induced Lung Injury Am. J. Respir. Crit. Care Med., August 1, 2005; 172(3): 334 - 343. [Abstract] [Full Text] [PDF]

				K.-J. Bai, A. P. Spicer, M. M. Mascarenhas, L. Yu, C. D. Ochoa, H. G. Garg, and D. A. Quinn The Role of Hyaluronan Synthase 3 in Ventilator-induced Lung Injury Am. J. Respir. Crit. Care Med., July 1, 2005; 172(1): 92 - 98. [Abstract] [Full Text] [PDF]

				P. G. Arndt, S. K. Young, J. G. Lieber, M. B. Fessler, J. A. Nick, and G. S. Worthen Inhibition of c-Jun N-Terminal Kinase Limits Lipopolysaccharide-induced Pulmonary Neutrophil Influx Am. J. Respir. Crit. Care Med., May 1, 2005; 171(9): 978 - 986. [Abstract] [Full Text] [PDF]

				M. R. Wilson, S. Choudhury, and M. Takata Pulmonary inflammation induced by high-stretch ventilation is mediated by tumor necrosis factor signaling in mice Am J Physiol Lung Cell Mol Physiol, April 1, 2005; 288(4): L599 - L607. [Abstract] [Full Text] [PDF]

				D. Angus, A. Ishizaka, M. Matthay, F. Lemaire, W. MacNee, and E. Abraham Critical Care in AJRCCM 2004 Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 537 - 544. [Full Text] [PDF]