Time-course of antigen-induced airway inflammation in the guinea-pig and its relationship to airway hyperresponsiveness

The causative relationship between airway inflammation and hyperreactivity is unclear, since inflammatory changes have been examined at one or, at most, a few time-points after antigen challenge in both human asthma and animal models. We have made a detailed investigation of inflammatory and functional changes in the airways up to 8 days after antigen challenge in guinea-pigs. In particular, we examined the hypothesis that eosinophil-derived mediators contribute to tissue damage and the development of airway hyperresponsiveness. Following antigen challenge, the influx of inflammatory cells and mediator release in airway tissue and bronchoalveolar lavage fluid were correlated temporally with histopathological changes in airway tissue and airway responsiveness. Eosinophil influx was demonstrable at 4 h. Eosinophilia peaked after 24 h and persisted for at least 8 days. Parallel increases in the concentrations of major basic protein and eosinophil cationic protein in bronchoalveolar lavage fluid indicated that the eosinophils were activated. Eosinophilia was accompanied by subepithelial oedema and epithelial damage co-localized with major basic protein immunoreactivity. A transient neutrophilia (< 48 h duration) and an increase in neutrophil elastase in bronchoalveolar lavage fluid peaked at 14 h. The proportion of airway macrophages with an activated morphology increased at 8 h and remained markedly elevated until 72 h. Airways were hyperresponsive to histamine at 4 h and for at least 8 days. The antigen-induced airway inflammation resemble in time-course and histopathology that seen in antigen-challenged asthmatics, and indicate that the eosinophil and its cytotoxic proteins may be major mediators of airway mucosal damage and airway hyperresponsiveness.

This article has been cited by other articles:

				H. Abdala-Valencia, J. Earwood, S. Bansal, M. Jansen, G. Babcock, B. Garvy, M. Wills-Karp, and J. M. Cook-Mills Nonhematopoietic NADPH oxidase regulation of lung eosinophilia and airway hyperresponsiveness in experimentally induced asthma Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1111 - L1125. [Abstract] [Full Text] [PDF]

				Y. Li, L. D. Martin, M. Minnicozzi, S. Greenfeder, J. Fine, C. A. Pettersen, B. Chorley, and K. B. Adler Enhanced Expression of Mucin Genes in a Guinea Pig Model of Allergic Asthma Am. J. Respir. Cell Mol. Biol., November 1, 2001; 25(5): 644 - 651. [Abstract] [Full Text] [PDF]

				K. L. Denzler, M. T. Borchers, J. R. Crosby, G. Cieslewicz, E. M. Hines, J. P. Justice, S. A. Cormier, K. A. Lindenberger, W. Song, W. Wu, et al. Extensive Eosinophil Degranulation and Peroxidase-Mediated Oxidation of Airway Proteins Do Not Occur in a Mouse Ovalbumin-Challenge Model of Pulmonary Inflammation J. Immunol., August 1, 2001; 167(3): 1672 - 1682. [Abstract] [Full Text] [PDF]

				D. R. Bergren Chronic tobacco smoke exposure increases airway sensitivity to capsaicin in awake guinea pigs J Appl Physiol, February 1, 2001; 90(2): 695 - 704. [Abstract] [Full Text] [PDF]

				M. Zaitsu, Y. Hamasaki, M. Matsuo, A. Kukita, K. Tsuji, M. Miyazaki, R. Hayasaki, E. Muro, S. Yamamoto, I. Kobayashi, et al. New induction of leukotriene A4 hydrolase by interleukin-4 and interleukin-13 in human polymorphonuclear leukocytes Blood, July 15, 2000; 96(2): 601 - 609. [Abstract] [Full Text] [PDF]

				M. Suzuki, R. Taha, D. Ihaku, Q. Hamid, and J. G. Martin CD8+ T Cells Modulate Late Allergic Airway Responses in Brown Norway Rats J. Immunol., November 15, 1999; 163(10): 5574 - 5581. [Abstract] [Full Text] [PDF]

				M. H. Vargas, L. Romero, B. Sommer, P. Zamudio, P. Gustin, and L. M. Montano Chronic exposure to ozone causes tolerance to airway hyperresponsiveness in guinea pigs: lack of SOD role J Appl Physiol, May 1, 1998; 84(5): 1749 - 1755. [Abstract] [Full Text] [PDF]