MJ Woolley, JA Denburg, R Ellis, M Dahlback and PM O'Byrne
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Airway inflammation is implicated in the pathogenesis of the airway hyperresponsiveness in asthma. An increased production of inflammatory cell progenitors may contribute to asthmatic airway inflammation. Although the number of circulating inflammatory cell progenitors in asthmatic subjects increases after allergen inhalation, no direct evidence exists for increased bone marrow progenitor production. We examined the effect of allergen inhalation on bone marrow progenitor production in seven dogs that develop allergen-induced airway hyperresponsiveness. The effect of inhaled budesonide, a corticosteroid known to be effective in the treatment of asthma, on allergen-induced bone marrow progenitor production and airway hyperresponsiveness was also examined. Allergen inhalation increased airway responsiveness (P < 0.001) and the number of granulocyte-macrophage colony-forming units (CFU) when cultured with dog serum and either recombinant canine stem cell factor (rcSCF) (P < 0.001) or granulocyte colony-stimulating factor (rcG-CSF) (P = 0.035). Budesonide treatment reduced the allergen- induced increases in airway responsiveness (P = 0.005) and abolished the allergen-induced increases in the numbers of CFU cultured with dog serum and either rcSCF (P < 0.001) or rcG-CSF (P = 0.009). These findings provide the first direct evidence that allergen inhalation increases bone marrow progenitor production and suggest that such increases may contribute to the development of airway hyperresponsiveness in asthma. In addition, the effectiveness of inhaled corticosteroids in asthma may result, in part, from their ability to suppress bone marrow production of inflammatory cells.

This article has been cited by other articles:

				S. Sergejeva, A.-K. Johansson, C. Malmhall, and J. Lotvall Allergen exposure-induced differences in CD34+ cell phenotype: relationship to eosinophilopoietic responses in different compartments Blood, February 15, 2004; 103(4): 1270 - 1277. [Abstract] [Full Text] [PDF]

				L. J. Wood, R. Sehmi, S. Dorman, Q. Hamid, M. K. Tulic, R. M. Watson, R. Foley, P. Wasi, J. A. Denburg, G. Gauvreau, et al. Allergen-induced Increases in Bone Marrow T Lymphocytes and Interleukin-5 Expression in Subjects with Asthma Am. J. Respir. Crit. Care Med., September 15, 2002; 166(6): 883 - 889. [Abstract] [Full Text]

				G. M. GAUVREAU, L. J. WOOD, R. SEHMI, R. M. WATSON, S. C. DORMAN, R. P. SCHLEIMER, J. A. DENBURG, and P. M. O'BYRNE The Effects of Inhaled Budesonide on Circulating Eosinophil Progenitors and Their Expression of Cytokines after Allergen Challenge in Subjects with Atopic Asthma Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2139 - 2144. [Abstract] [Full Text]

				L. Xu, R. Olivenstein, J. G. Martin, and W. S. Powell Inhaled budesonide inhibits OVA-induced airway narrowing, inflammation, and cys-LT synthesis in BN rats J Appl Physiol, November 1, 2000; 89(5): 1852 - 1858. [Abstract] [Full Text] [PDF]

				M. Tomaki, L.-L. Zhao, J. Lundahl, M. Sjostrand, M. Jordana, A. Linden, P. O'Byrne, and J. Lotvall Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor {alpha} J. Immunol., October 1, 2000; 165(7): 4040 - 4050. [Abstract] [Full Text] [PDF]

				J. A Denburg Haemopoietic mechanisms in nasal polyposis and asthma Thorax, October 1, 2000; 55(90002): 24S - 25. [Full Text]

				P. S. Foster Allergic Networks Regulating Eosinophilia Am. J. Respir. Cell Mol. Biol., October 1, 1999; 21(4): 451 - 454. [Full Text]

				M. D. Inman, R. Ellis, J. Wattie, J. A. Denburg, and P. M. O'Byrne Allergen-Induced Increase in Airway Responsiveness, Airway Eosinophilia, and Bone-Marrow Eosinophil Progenitors in Mice Am. J. Respir. Cell Mol. Biol., October 1, 1999; 21(4): 473 - 479. [Abstract] [Full Text]

				R J Meijer, H A M Kerstjens, L R Arends, H F Kauffman, G H Koëter, and D S Postma Effects of inhaled fluticasone and oral prednisolone on clinical and inflammatory parameters in patients with asthma Thorax, October 1, 1999; 54(10): 894 - 899. [Abstract] [Full Text]

				B. N. Lambrecht, I. Carro-Muino, K. Vermaelen, and R. A. Pauwels Allergen-Induced Changes in Bone-Marrow Progenitor and Airway Dendritic Cells in Sensitized Rats Am. J. Respir. Cell Mol. Biol., June 1, 1999; 20(6): 1165 - 1174. [Abstract] [Full Text]

				L. J. WOOD, R. SEHMI, G. M. GAUVREAU, R. M. WATSON, R. FOLEY, J. A. DENBURG, and P. M. O'BYRNE An Inhaled Corticosteroid, Budesonide, Reduces Baseline but Not Allergen-induced Increases in Bone Marrow Inflammatory Cell Progenitors in Asthmatic Subjects Am. J. Respir. Crit. Care Med., May 1, 1999; 159(5): 1457 - 1463. [Abstract] [Full Text] [PDF]

				L. J. Wood, M. D. Inman, J. A. Denburg, and P. M. O'Byrne Allergen Challenge Increases Cell Traffic between Bone Marrow and Lung Am. J. Respir. Cell Mol. Biol., June 1, 1998; 18(6): 759 - 767. [Abstract] [Full Text]

				J. P.B. Viola, A. Kiani, P. T. Bozza, and A. Rao Regulation of Allergic Inflammation and Eosinophil Recruitment in Mice Lacking the Transcription Factor NFAT1: Role of Interleukin-4 (IL-4) and IL-5 Blood, April 1, 1998; 91(7): 2223 - 2230. [Abstract] [Full Text] [PDF]

				L. J. WOOD, M. D. INMAN, R. M. WATSON, R. FOLEY, J. A. DENBURG, and P. M. O'BYRNE Changes in Bone Marrow Inflammatory Cell Progenitors after Inhaled Allergen in Asthmatic Subjects Am. J. Respir. Crit. Care Med., January 1, 1998; 157(1): 99 - 105. [Abstract] [Full Text] [PDF]

				L. J. Janssen, I. McGrogan, J. Wattie, P. M. O'Byrne, and E. E. Daniel Myogenic and neurogenic mechanisms and arachidonate metabolites in bronchial muscle response to allergen Am J Physiol Lung Cell Mol Physiol, December 1, 1997; 273(6): L1118 - L1125. [Abstract] [Full Text] [PDF]

				M. D. Inman, J. A. Denburg, R. Ellis, M. Dahlbäck, and P. M. O'Byrne The Effect of Treatment with Budesonide or PGE2 In Vitro on Allergen-induced Increases in Canine Bone Marrow Progenitors Am. J. Respir. Cell Mol. Biol., November 1, 1997; 17(5): 634 - 641. [Abstract] [Full Text]

				M. I. C. Gaspar Elsas, D. Joseph, P. Xavier Elsas, and B. Boris Vargaftig Rapid Increase in Bone-marrow Eosinophil Production and Responses to Eosinopoietic Interleukins Triggered by Intranasal Allergen Challenge Am. J. Respir. Cell Mol. Biol., October 1, 1997; 17(4): 404 - 413. [Abstract] [Full Text]

				B. B. VARGAFTIG Modifications of Experimental Bronchopulmonary Hyperresponsiveness Am. J. Respir. Crit. Care Med., October 1, 1997; 156(4): S97 - S102. [Abstract] [Full Text] [PDF]