J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/08/449/06 $2.00
Volume 186, Number 3, August 4, 1997 449-454

BRIEF DEFINITIVE REPORT:
Development of Eosinophilic Airway Inflammation and Airway Hyperresponsiveness in Mast Cell-deficient Mice

By K. Takeda,^* E. Hamelmann,^* A. Joetham,^* L.D. Shultz,^§ G.L. Larsen,^* C.G. Irvin, and E.W. Gelfand^*

From the ^* Division of Basic Sciences and Pulmonary Medicine, Department of Pediatrics, and the  Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado; and ^§ The Jackson Laboratory, Bar Harbor, Maine

Mast cells are the main effector cells of immediate hypersensitivity and anaphylaxis. Their role in the development of allergen-induced airway hyperresponsiveness (AHR) is controversial and based on indirect evidence. To address these issues, mast cell-deficient mice (W/W  ^v) and their congenic littermates were sensitized to ovalbumin (OVA) by intraperitoneal injection and subsequently challenged with OVA via the airways. Comparison of OVA-specific immunoglobulin E (IgE) levels in the serum and numbers of eosinophils in bronchoalveolar lavage fluid or lung digests showed no differences between the two groups of mice. Further, measurements of airway resistance and dynamic compliance at baseline and after inhalation of methacholine were similar. These data indicate that mast cells or IgE-mast cell activation is not required for the development of eosinophilic inflammation and AHR in mice sensitized to allergen via the intraperitoneal route and challenged via the airways.

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• Rha, Y.-H., Taube, C., Haczku, A., Joetham, A., Takeda, K., Duez, C., Siegel, M., Aydintug, M. K., Born, W. K., Dakhama, A., Gelfand, E. W. (2002). Effect of Microbial Heat Shock Proteins on Airway Inflammation and Hyperresponsiveness. J. Immunol. 169: 5300-5307 [Abstract] [Full Text]  
• Andrews, R. P., Ericksen, M. B., Cunningham, C. M., Daines, M. O., Hershey, G. K. K. (2002). Analysis of the Life Cycle of Stat6. CONTINUOUS CYCLING OF STAT6 IS REQUIRED FOR IL-4 SIGNALING. J. Biol. Chem. 277: 36563-36569 [Abstract] [Full Text]  
• Mayr, S. I., Zuberi, R. I., Zhang, M., de Sousa-Hitzler, J., Ngo, K., Kuwabara, Y., Yu, L., Fung-Leung, W.-P., Liu, F.-T. (2002). IgE-Dependent Mast Cell Activation Potentiates Airway Responses in Murine Asthma Models. J. Immunol. 169: 2061-2068 [Abstract] [Full Text]  
• Tomioka, S., Bates, J. H. T., Irvin, C. G. (2002). Airway and tissue mechanics in a murine model of asthma: alveolar capsule vs. forced oscillations. J. Appl. Physiol. 93: 263-270 [Abstract] [Full Text]  
• Gelfand, E. W. (2002). Mice Are a Good Model of Human Airway Disease. Am. J. Respir. Crit. Care Med. 166: 5-6 [Full Text]  
• Lahn, M., Kanehiro, A., Takeda, K., Terry, J., Hahn, Y.-S., Aydintug, M. K., Konowal, A., Ikuta, K., O'Brien, R. L., Gelfand, E. W., Born, W. K. (2002). MHC class I-dependent Vgamma 4+ pulmonary T cells regulate alpha beta T cell-independent airway responsiveness. Proc. Natl. Acad. Sci. USA 99: 8850-8855 [Abstract] [Full Text]  
• Wagers, S., Lundblad, L., Moriya, H. T., Bates, J. H. T., Irvin, C. G. (2002). Nonlinearity of respiratory mechanics during bronchoconstriction in mice with airway inflammation. J. Appl. Physiol. 92: 1802-1807 [Abstract] [Full Text]  
• Dakhama, A., Kanehiro, A., Makela, M. J., Loader, J. E., Larsen, G. L., Gelfand, E. W. (2002). Regulation of Airway Hyperresponsiveness by Calcitonin Gene-related Peptide in Allergen Sensitized and Challenged Mice. Am. J. Respir. Crit. Care Med. 165: 1137-1144 [Abstract] [Full Text]  
• Crosby, J. R., Cieslewicz, G., Borchers, M., Hines, E., Carrigan, P., Lee, J. J., Lee, N. A. (2002). Early Phase Bronchoconstriction in the Mouse Requires Allergen-Specific IgG. J. Immunol. 168: 4050-4054 [Abstract] [Full Text]  
• Poynter, M. E., Irvin, C. G., Janssen-Heininger, Y. M. W. (2002). Rapid Activation of Nuclear Factor-{kappa}B in Airway Epithelium in a Murine Model of Allergic Airway Inflammation. Am. J. Pathol. 160: 1325-1334 [Abstract] [Full Text]  
• Humbles, A. A., Lu, B., Friend, D. S., Okinaga, S., Lora, J., Al-garawi, A., Martin, T. R., Gerard, N. P., Gerard, C. (2002). The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. Proc. Natl. Acad. Sci. USA 99: 1479-1484 [Abstract] [Full Text]  
• Crosby, J. R., Shen, H. H., Borchers, M. T., Justice, J. P., Ansay, T., Lee, J. J., Lee, N. A. (2002). Ectopic expression of IL-5 identifies an additional CD4+ T cell mechanism of airway eosinophil recruitment. Am. J. Physiol. Lung Cell. Mol. Physiol. 282: L99-L108 [Abstract] [Full Text]  
• Page, S., Ammit, A. J., Black, J. L., Armour, C. L. (2001). Human mast cell and airway smooth muscle cell interactions: implications for asthma. Am. J. Physiol. Lung Cell. Mol. Physiol. 281: L1313-L1323 [Abstract] [Full Text]  
• Kung, T. T., Luo, B., Crawley, Y., Garlisi, C. G., Devito, K., Minnicozzi, M., Egan, R. W., Kreutner, W., Chapman, R. W. (2001). Effect of Anti-mIL-9 Antibody on the Development of Pulmonary Inflammation and Airway Hyperresponsiveness in Allergic Mice. Am. J. Respir. Cell Mol. Bio. 25: 600-605 [Abstract] [Full Text]  
• Takeda, K., Haczku, A., Lee, J. J., Irvin, C. G., Gelfand, E. W. (2001). Strain dependence of airway hyperresponsiveness reflects differences in eosinophil localization in the lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 281: L394-L402 [Abstract] [Full Text]  
• Oliveira, S. H. P., Hogaboam, C. M., Berlin, A., Lukacs, N. W. (2001). SCF-induced airway hyperreactivity is dependent on leukotriene production. Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L1242-L1249 [Abstract] [Full Text]  
• Tournoy, K. G., Kips, J. C., Pauwels, R. A. (2001). The Allergen-Induced Airway Hyperresponsiveness in a Human-Mouse Chimera Model of Asthma Is T Cell and IL-4 and IL-5 Dependent. J. Immunol. 166: 6982-6991 [Abstract] [Full Text]  
• Tomkinson, A., Duez, C., Cieslewicz, G., Pratt, J. C., Joetham, A., Shanafelt, M.-C., Gundel, R., Gelfand, E. W. (2001). A Murine IL-4 Receptor Antagonist That Inhibits IL-4- and IL-13-Induced Responses Prevents Antigen-Induced Airway Eosinophilia and Airway Hyperresponsiveness. J. Immunol. 166: 5792-5800 [Abstract] [Full Text]  
• TOMKINSON, A., CIESLEWICZ, G., DUEZ, C., LARSON, K. A., LEE, J. J., GELFAND, E. W. (2001). Temporal Association between Airway Hyperresponsiveness and Airway Eosinophilia in Ovalbumin-Sensitized Mice. Am. J. Respir. Crit. Care Med. 163: 721-730 [Abstract] [Full Text]  
• KANEHIRO, A., IKEMURA, T., MÄKELÄ, M. J., LAHN, M., JOETHAM, A., DAKHAMA, A., GELFAND, E. W. (2001). Inhibition of Phosphodiesterase 4 Attenuates Airway Hyperresponsiveness and Airway Inflammation in a Model of Secondary Allergen Challenge. Am. J. Respir. Crit. Care Med. 163: 173-184 [Abstract] [Full Text]  
• Malaviya, R., Chen, C.-L., Navara, C., Malaviya, R., Liu, X.-P., Keenan, M., Waurzyniak, B., Uckun, F. M. (2000). Treatment of Allergic Asthma by Targeting Janus Kinase 3-Dependent Leukotriene Synthesis in Mast Cells with 4-(3',5'-Dibromo-4'-hydroxyphenyl)amino-6,7-dimethoxyquinazoline (WHI-P97). J. Pharmacol. Exp. Ther. 295: 912-926 [Abstract] [Full Text]  
• MacLean, J. A., De Sanctis, G. T., Ackerman, K. G., Drazen, J. M., Sauty, A., DeHaan, E., Green, F. H. Y., Charo, I. F., Luster, A. D. (2000). CC Chemokine Receptor-2 Is Not Essential for the Development of Antigen-Induced Pulmonary Eosinophilia and Airway Hyperresponsiveness. J. Immunol. 165: 6568-6575 [Abstract] [Full Text]  
• Hamelmann, E., Takeda, K., Haczku, A., Cieslewicz, G., Shultz, L., Hamid, Q., Xing, Z., Gauldie, J., Gelfand, E. W. (2000). Interleukin (IL)-5 but Not Immunoglobulin E Reconstitutes Airway Inflammation and Airway Hyperresponsiveness in IL-4-Deficient Mice. Am. J. Respir. Cell Mol. Bio. 23: 327-334 [Abstract] [Full Text]  
• KANEHIRO, A., TAKEDA, K., JOETHAM, A., TOMKINSON, A., IKEMURA, T., IRVIN, C. G., GELFAND, E. W. (2000). Timing of Administration of Anti-VLA-4 Differentiates Airway Hyperresponsiveness in the Central and Peripheral Airways in Mice. Am. J. Respir. Crit. Care Med. 162: 1132-1139 [Abstract] [Full Text]  
• KIPS, J. C., TOURNOY, K. G., PAUWELS, R. A. (2000). Gene Knockout Models of Asthma. Am. J. Respir. Crit. Care Med. 162: S66-70 [Full Text]  
• Williams, C. M.M., Galli, S. J. (2000). Mast Cells Can Amplify Airway Reactivity and Features of Chronic Inflammation in an Asthma Model in Mice. JEM 192: 455-462 [Abstract] [Full Text]  
• Volgyesi, G. A., Tremblay, L. N., Webster, P., Zamel, N., Slutsky, A. S. (2000). A new ventilator for monitoring lung mechanics in small animals. J. Appl. Physiol. 89: 413-421 [Abstract] [Full Text]  
• KNOTT, P. G., GATER, P. R., BERTRAND, C. P. (2000). Airway Inflammation Driven by Antigen-specific Resident Lung CD4+ T Cells in alpha beta -T Cell Receptor Transgenic Mice. Am. J. Respir. Crit. Care Med. 161: 1340-1348 [Abstract] [Full Text]  
• Kobayashi, T., Miura, T., Haba, T., Sato, M., Serizawa, I., Nagai, H., Ishizaka, K. (2000). An Essential Role of Mast Cells in the Development of Airway Hyperresponsiveness in a Murine Asthma Model. J. Immunol. 164: 3855-3861 [Abstract] [Full Text]  

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