P Padrid, S Snook, T Finucane, P Shiue, P Cozzi, J Solway and AR Leff
Department of Medicine, University of Chicago, IL 60637.

We studied the effect of chronic immune sensitization on the airway reactivity and associated cytologic and histologic alterations in initially nonatopic cats, a species that spontaneously develops idiopathic asthma. Seven cats were sensitized by intramuscular injection of Ascaris suum antigen (AA) for 4 wk, and four other cats served as sham controls. Airway sensitization was demonstrated by an increased response to nebulized AA in sensitized animals (RL = 45.9 +/- 6.1 cm H2O/L/s, versus a baseline response of 24.7 +/- 1.5 cm H2O/L/s, p < 0.01), and hyperresponsiveness was demonstrated by an increased response to acetylcholine (ACh)-challenge 24 h after AA (approximately 1.0 log decrease in PD200, p < 0.01). The number of eosinophils in the sensitized animals' bronchoalveolar lavage (BAL) fluid increased 12- fold (p < 0.01 versus control) in response to AA challenge; 32 +/- 5% of the BAL eosinophils had a specific density < 1.050, versus 8 +/- 2% prior to AA challenge (p < 0.05). There was no change in airway reactivity, eosinophil recovery, or density in the control group 24 h after sham challenge with saline. The same seven sensitized cats further received nebulized AA three times weekly for 4 to 6 wk, after which BAL samples were again obtained and ACh dose-response curves generated 72 h after the final administration of nebulized AA. Airway hyperresponsiveness increased (approximately 1.5 log decrease in PD200, p < 0.001) and the number of eosinophils recovered in BAL fluid was increased 11-fold (p < 0.05). Necropsy specimens demonstrated bronchoconstriction in AA-challenged animals but not controls; luminal narrowing was accompanied by: (1) a 29.0 +/- 0.34% increase in smooth- muscle thickness (p < 0.05); (2) goblet-cell and submucosal-gland hypertrophy and hyperplasia; and (3) epithelial erosion and eosinophilic infiltration. We demonstrate in nonhuman species persistent airway hyperreactivity associated with a complete constellation of histologic changes in epithelium, smooth muscle, and mucus glands, and cytologic changes in BAL fluid, all induced by immune sensitization. Our data suggest that chronic immune sensitization per se could be a salient factor in causing many of the changes associated with chronic bronchial asthma.

This article has been cited by other articles:

				E. D. Fixman, A. Stewart, and J. G. Martin Basic mechanisms of development of airway structural changes in asthma Eur. Respir. J., February 1, 2007; 29(2): 379 - 389. [Abstract] [Full Text] [PDF]

				P. Padrid Use of Inhaled Medications to Treat Respiratory Diseases in Dogs and Cats J. Am. Anim. Hosp. Assoc., March 1, 2006; 42(2): 165 - 169. [Abstract] [Full Text] [PDF]

				K. Nagao, H. Tanaka, M. Komai, T. Masuda, S. Narumiya, and H. Nagai Role of Prostaglandin I2 in Airway Remodeling Induced by Repeated Allergen Challenge in Mice Am. J. Respir. Cell Mol. Biol., September 1, 2003; 29(3): 314 - 320. [Abstract] [Full Text] [PDF]

				K. F. Xu, R. Vlahos, A. Messina, T. L. Bamford, J. F. Bertram, and A. G. Stewart Antigen-induced airway inflammation in the Brown Norway rat results in airway smooth muscle hyperplasia J Appl Physiol, November 1, 2002; 93(5): 1833 - 1840. [Abstract] [Full Text] [PDF]

				D.J. Turner, P.R. Gray, S.A. Taylor, J. Thomas, and H.W. Mitchell Physiological responses of the airway wall and lung in hyperresponsive pigs Eur. Respir. J., December 1, 2001; 18(6): 935 - 941. [Abstract] [Full Text] [PDF]

				A. Trifilieff, A. El-Hashim, and C. Bertrand Time course of inflammatory and remodeling events in a murine model of asthma: effect of steroid treatment Am J Physiol Lung Cell Mol Physiol, December 1, 2000; 279(6): L1120 - L1128. [Abstract] [Full Text] [PDF]

				A. R Leff Role of leukotrienes in bronchial hyperresponsiveness and cellular responses in airways Thorax, October 1, 2000; 55(90002): 32S - 37. [Full Text]

				P. Kesteven Traveller's thrombosis Thorax, August 1, 2000; 55(90001): S32 - 36. [PDF]

				A. R. LEFF Role of Leukotrienes in Bronchial Hyperresponsiveness and Cellular Responses in Airways Am. J. Respir. Crit. Care Med., February 1, 2000; 161(2): S125 - 132. [Full Text] [PDF]

				M. E. Zacour and J. G. Martin Protein kinase C is involved in enhanced airway smooth muscle cell growth in hyperresponsive rats Am J Physiol Lung Cell Mol Physiol, January 1, 2000; 278(1): L59 - L67. [Abstract] [Full Text] [PDF]

				J. Temelkovski, S. P Hogan, D. P Shepherd, P. S Foster, and R. K Kumar An improved murine model of asthma: selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen Thorax, October 1, 1998; 53(10): 849 - 856. [Abstract] [Full Text]

				P. A. Padrid, M. Mathur, X. Li, K. Herrmann, Y. Qin, A. Cattamanchi, J. Weinstock, D. Elliott, A. I. Sperling, and J. A. Bluestone CTLA4Ig Inhibits Airway Eosinophilia and Hyperresponsiveness by Regulating the Development of Th1/Th2 Subsets in a Murine Model of Asthma Am. J. Respir. Cell Mol. Biol., April 1, 1998; 18(4): 453 - 462. [Abstract] [Full Text]