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Am. J. Respir. Crit. Care Med., Volume 156, Number 3, September 1997, 766-775

Noninvasive Measurement of Airway Responsiveness in Allergic Mice Using Barometric Plethysmography

E. HAMELMANN, J. SCHWARZE, K. TAKEDA, A. OSHIBA, G. L. LARSEN, C. G. IRVIN, and E. W. GELFAND

Divisions of Basic Sciences and Pulmonary Medicine, Department of Pediatrics; and Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado

To study the mechanisms and kinetics underlying the development of increased airway responsiveness (AR) after allergic sensitization, animal models have been invaluable. Using barometric whole-body plethysmography and increases in enhanced pause (Penh) as an index of airway obstruction, we measured responses to inhaled methacholine in conscious, unrestrained mice after sensitization and airway challenge with ovalbumin (OVA). Sensitized and challenged animals had significantly increased AR to aerosolized methacholine compared with control animals. AR measured as Penh was associated with increased IgE production and eosinophil lung infiltration. In a separate approach we confirmed the involvement of the lower airways in the response to aerosolized methacholine using tracheotomized mice. Increases in Penh values after methacholine challenge were also correlated with increased intrapleural pressure, measured via an esophageal tube. Lastly, mice demonstrating AR using a noninvasive technique also demonstrated increased pulmonary resistance responses to aerosolized methacholine when measured using an invasive technique the following day in the same animals. The increases in Penh values were inhibited by pretreatment of the mice with a beta 2-agonist. These data indicate that measurement of AR to inhaled methacholine by barometric whole-body plethysmography is a valid indicator of airway hyperresponsiveness after allergic sensitization in mice. The measurement of AR in unrestrained, conscious animals provides new opportunities to evaluate the mechanisms and kinetics underlying the development and maintenance of airway hyperresponsiveness and to assess various therapeutic interventions.




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M. Yang, D. Rangasamy, K. I. Matthaei, A. J. Frew, N. Zimmmermann, S. Mahalingam, D. C. Webb, D. J. Tremethick, P. J. Thompson, S. P. Hogan, et al.
Inhibition of Arginase I Activity by RNA Interference Attenuates IL-13-Induced Airways Hyperresponsiveness
J. Immunol., October 15, 2006; 177(8): 5595 - 5603.
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J. Maatta, M. Lehto, M. Leino, S. Tillander, R. Haapakoski, M.-L. Majuri, H. Wolff, S. Rautio, I. Welling, K. Husgafvel-Pursiainen, et al.
Mechanisms of Particle-Induced Pulmonary Inflammation in a Mouse Model: Exposure to Wood Dust
Toxicol. Sci., September 1, 2006; 93(1): 96 - 104.
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 Am. J. Respir. Cell Mol. Bio.Home page
A. Hirano, A. Kanehiro, K. Ono, W. Ito, A. Yoshida, C. Okada, H. Nakashima, Y. Tanimoto, M. Kataoka, E. W. Gelfand, et al.
Pirfenidone Modulates Airway Responsiveness, Inflammation, and Remodeling after Repeated Challenge
Am. J. Respir. Cell Mol. Biol., September 1, 2006; 35(3): 366 - 377.
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M. Witzenrath, B. Ahrens, S. M. Kube, A. Braun, H. G. Hoymann, A. C. Hocke, S. Rosseau, N. Suttorp, E. Hamelmann, and H. Schutte
Detection of allergen-induced airway hyperresponsiveness in isolated mouse lungs
Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L466 - L472.
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M. Witzenrath, B. Ahrens, S. M. Kube, A. C. Hocke, S. Rosseau, E. Hamelmann, N. Suttorp, and H. Schutte
Allergic lung inflammation induces pulmonary vascular hyperresponsiveness
Eur. Respir. J., August 1, 2006; 28(2): 370 - 377.
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N. Wang, M. Campo, L. Ting, C. Fleming, C. Terhorst, and P. W. Finn
The Costimulatory Molecule SLAM Is Critical for Pulmonary Allergic Responses
Am. J. Respir. Cell Mol. Biol., August 1, 2006; 35(2): 206 - 210.
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C. S. Bakshi, M. Malik, P. M. Carrico, and T. J. Sellati
T-bet Deficiency Facilitates Airway Colonization by Mycoplasma pulmonis in a Murine Model of Asthma
J. Immunol., August 1, 2006; 177(3): 1786 - 1795.
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Z. Yin, L. Gonzales, V. Kolla, N. Rath, Y. Zhang, M. M. Lu, S. Kimura, P. L. Ballard, M. F. Beers, J. A. Epstein, et al.
Hop functions downstream of Nkx2.1 and GATA6 to mediate HDAC-dependent negative regulation of pulmonary gene expression
Am J Physiol Lung Cell Mol Physiol, August 1, 2006; 291(2): L191 - L199.
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P. J. Dunford, N. O'Donnell, J. P. Riley, K. N. Williams, L. Karlsson, and R. L. Thurmond
The Histamine H4 Receptor Mediates Allergic Airway Inflammation by Regulating the Activation of CD4+ T Cells.
J. Immunol., June 1, 2006; 176(11): 7062 - 7070.
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 Physiol. GenomicsHome page
A. C. Patel, J. D. Morton, E. Y. Kim, Y. Alevy, S. Swanson, J. Tucker, G. Huang, E. Agapov, T. E. Phillips, M. E. Fuentes, et al.
Genetic segregation of airway disease traits despite redundancy of calcium-activated chloride channel family members
Physiol Genomics, May 16, 2006; 25(3): 502 - 513.
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D. C. Kim, F. I. Hsu, N. A. Barrett, D. S. Friend, R. Grenningloh, I-C. Ho, A. Al-Garawi, J. M. Lora, B. K. Lam, K. F. Austen, et al.
Cysteinyl Leukotrienes Regulate Th2 Cell-Dependent Pulmonary Inflammation
J. Immunol., April 1, 2006; 176(7): 4440 - 4448.
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 Am. J. Respir. Crit. Care Med.Home page
W. R. Henderson Jr., G. K. S. Chiang, Y.-t. Tien, and E. Y. Chi
Reversal of Allergen-induced Airway Remodeling by CysLT1 Receptor Blockade
Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 718 - 728.
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A. August, C. Mueller, V. Weaver, T. A. Polanco, E. R. Walsh, and M. T. Cantorna
Nutrients, Nuclear Receptors, Inflammation, Immunity Lipids, PPAR, and Allergic Asthma
J. Nutr., March 1, 2006; 136(3): 695 - 699.
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S. J. Park, M. T. Wiekowski, S. A. Lira, and B. Mehrad
Neutrophils Regulate Airway Responses in a Model of Fungal Allergic Airways Disease
J. Immunol., February 15, 2006; 176(4): 2538 - 2545.
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E. Lopez, V. del Pozo, T. Miguel, B. Sastre, C. Seoane, E. Civantos, E. Llanes, M. L. Baeza, P. Palomino, B. Cardaba, et al.
Inhibition of Chronic Airway Inflammation and Remodeling by Galectin-3 Gene Therapy in a Murine Model
J. Immunol., February 1, 2006; 176(3): 1943 - 1950.
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 ThoraxHome page
M Peters, M Kauth, J Schwarze, C Korner-Rettberg, J Riedler, D Nowak, C Braun-Fahrlander, E von Mutius, A Bufe, O Holst, et al.
Inhalation of stable dust extract prevents allergen induced airway inflammation and hyperresponsiveness
Thorax, February 1, 2006; 61(2): 134 - 139.
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A. S. Leme, C. Hubeau, Y. Xiang, A. Goldman, K. Hamada, Y. Suzaki, and L. Kobzik
Role of Breast Milk in a Mouse Model of Maternal Transmission of Asthma Susceptibility
J. Immunol., January 15, 2006; 176(2): 762 - 769.
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N. E. Mangan, N. van Rooijen, A. N. J. McKenzie, and P. G. Fallon
Helminth-Modified Pulmonary Immune Response Protects Mice from Allergen-Induced Airway Hyperresponsiveness
J. Immunol., January 1, 2006; 176(1): 138 - 147.
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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
B. D. Medoff, A. M. Tager, R. Jackobek, T. K. Means, L. Wang, and A. D. Luster
Antibody-antigen interaction in the airway drives early granulocyte recruitment through BLT1
Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L170 - L178.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Papapetropoulos, D. C. M. Simoes, G. Xanthou, C. Roussos, and C. Gratziou
Soluble guanylyl cyclase expression is reduced in allergic asthma
Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L179 - L184.
[Abstract] [Full Text] [PDF]

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 JEMHome page
J. Kearley, J. E. Barker, D. S. Robinson, and C. M. Lloyd
Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent
J. Exp. Med., December 5, 2005; 202(11): 1539 - 1547.
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 Am. J. Pathol.Home page
R. Fischer, J. R. McGhee, H. L. Vu, T. P. Atkinson, R. J. Jackson, D. Tome, and P. N. Boyaka
Oral and Nasal Sensitization Promote Distinct Immune Responses and Lung Reactivity in a Mouse Model of Peanut Allergy
Am. J. Pathol., December 1, 2005; 167(6): 1621 - 1630.
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J. Zhang-Hoover, P. Finn, and J. Stein-Streilein
Modulation of Ovalbumin-Induced Airway Inflammation and Hyperreactivity by Tolerogenic APC
J. Immunol., December 1, 2005; 175(11): 7117 - 7124.
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P. Stock, O. Akbari, R. H. DeKruyff, and D. T. Umetsu
Respiratory Tolerance Is Inhibited by the Administration of Corticosteroids
J. Immunol., December 1, 2005; 175(11): 7380 - 7387.
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P. Smith, R. E. Fallon, N. E. Mangan, C. M. Walsh, M. Saraiva, J. R. Sayers, A. N.J. McKenzie, A. Alcami, and P. G. Fallon
Schistosoma mansoni secretes a chemokine binding protein with antiinflammatory activity
J. Exp. Med., November 21, 2005; 202(10): 1319 - 1325.
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 Toxicol SciHome page
C. C. Dong, X. J. Yin, J. Y. C. Ma, L. Millecchia, Z.-X. Wu, M. W. Barger, J. R. Roberts, J. M. Antonini, R. D. Dey, and J. K. H. Ma
Effect of Diesel Exhaust Particles on Allergic Reactions and Airway Responsiveness in Ovalbumin-Sensitized Brown Norway Rats
Toxicol. Sci., November 1, 2005; 88(1): 202 - 212.
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 Antimicrob. Agents Chemother.Home page
M. Fonseca-Aten, C. M. Salvatore, A. Mejias, A. M. Rios, S. Chavez-Bueno, K. Katz, A. M. Gomez, G. H. McCracken Jr, and R. D. Hardy
Evaluation of LBM415 (NVP PDF-713), a Novel Peptide Deformylase Inhibitor, for Treatment of Experimental Mycoplasma pneumoniae Pneumonia
Antimicrob. Agents Chemother., October 1, 2005; 49(10): 4128 - 4136.
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A. Fedulov, E. Silverman, Y. Xiang, A. Leme, and L. Kobzik
Immunostimulatory CpG Oligonucleotides Abrogate Allergic Susceptibility in a Murine Model of Maternal Asthma Transmission
J. Immunol., October 1, 2005; 175(7): 4292 - 4300.
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 Am. J. Respir. Crit. Care Med.Home page
C. Desmet, P. Gosset, E. Henry, V. Garze, P. Faisca, N. Vos, F. Jaspar, D. Melotte, B. Lambrecht, D. Desmecht, et al.
Treatment of Experimental Asthma by Decoy-mediated Local Inhibition of Activator Protein-1
Am. J. Respir. Crit. Care Med., September 15, 2005; 172(6): 671 - 678.
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 J. Pharmacol. Exp. Ther.Home page
K. M. Raehal, J. K. L. Walker, and L. M. Bohn
Morphine Side Effects in {beta}-Arrestin 2 Knockout Mice
J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1195 - 1201.
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 Am. J. Respir. Cell Mol. Bio.Home page
A. Robichaud, S. A. Tuck, S. Kargman, J. Tam, E. Wong, M. Abramovitz, J. Mortimer, H. E. Burston, P. Masson, J. Hirota, et al.
Gob-5 Is Not Essential for Mucus Overproduction in Preclinical Murine Models of Allergic Asthma
Am. J. Respir. Cell Mol. Biol., September 1, 2005; 33(3): 303 - 314.
[Abstract] [Full Text] [PDF]

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D Shoseyov, H Bibi, S Offer, O Schwob, M Krimsky, M Kleiman, and S Yedgar
Treatment of ovalbumin-induced experimental allergic bronchitis in rats by inhaled inhibitor of secretory phospholipase A2
Thorax, September 1, 2005; 60(9): 747 - 753.
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B. T. Ameredes, R. Zamora, J. M. Sethi, H.-L. Liu, L. K. Kohut, A. L. Gligonic, A. M. K. Choi, and W. J. Calhoun
Alterations in Nitric Oxide and Cytokine Production with Airway Inflammation in the Absence of IL-10
J. Immunol., July 15, 2005; 175(2): 1206 - 1213.
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M. Patel, D. Xu, P. Kewin, B. Choo-Kang, C. McSharry, N. C. Thomson, and F. Y. Liew
TLR2 Agonist Ameliorates Established Allergic Airway Inflammation by Promoting Th1 Response and Not via Regulatory T Cells
J. Immunol., June 15, 2005; 174(12): 7558 - 7563.
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 J. Appl. Physiol.Home page
S. J. Lai-Fook and Y.-L. Lai
Airway resistance due to alveolar gas compression measured by barometric plethysmography in mice
J Appl Physiol, June 1, 2005; 98(6): 2204 - 2218.
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J. Schwarze, E. Hamelmann, E. W. Gelfand, A. Adler, G. Cieslewicz, and C. G. Irvin
Barometric whole body plethysmography in mice
J Appl Physiol, May 1, 2005; 98(5): 1955 - 1957.
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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
B. T. Ameredes, J. M. Sethi, H.-L. Liu, A. M. K. Choi, and W. J. Calhoun
Enhanced nitric oxide production associated with airway hyporesponsiveness in the absence of IL-10
Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L868 - L873.
[Abstract] [Full Text] [PDF]


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