Am. J. Respir. Cell Mol. Biol., Volume 18, Number 6, June, 1998 759-767

Allergen Challenge Increases Cell Traffic between Bone Marrow and Lung

Lorna J. Wood, Mark D. Inman, Judah A. Denburg, and Paul M. O'Byrne

Asthma Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Increases in inflammatory-cell progenitors have been demonstrated in the bone marrow (BM) after inhalation of Ascaris suum in dogs at the time of allergen-induced airway hyperresponsiveness (AHR). The aim of this study was to evaluate the effect of allergen challenge on trafficking of inflammatory cells and their progenitors from the BM to the lung, using a marker of proliferating cells, bromodeoxyuridine (BrdU). BrdU is a thymidine analogue taken up by the DNA of dividing cells, and can be detected with immunohistochemistry (IHC). The development of AHR was assessed through acetylcholine (ACh) airway responsiveness before and after allergen inhalation. Two groups of dogs were matched for the degree of AHR after a screening allergen challenge. On the study day, one group inhaled allergen (n = 8) and one group inhaled diluent (n = 8). All dogs received equal bolus injections of BrdU before and at 5 h after challenge. Blood samples were taken before challenge and at 5 h and 24 h after challenge, and BM aspirate and bronchoalveolar lavage (BAL) samples were taken 24 h after challenge. BrdU-positive cells were detected in cytospin preparations of these samples, using IHC. Allergen inhalation caused AHR (P < 0.05) at 24 h after allergen challenge, and also an increase in BrdU-positive cells in blood, which was 5.7 ± 0.6% (mean ± SEM) after allergen challenge and 2.5 ± 0.7% after diluent (P < 0.005); in BM the increase in BrdU-positive cells was 27.0 ± 3.4% after allergen challenge and 18.9 ± 3.2% after diluent (P = 0.1); and in BAL the increase was 3.2 ± 0.4% after allergen challenge and 0.8 ± 0.3% after diluent (P < 0.005). There was a significant correlation between the number of BAL neutrophils and the percentage of BrdU-positive BAL cells (r² = 0.54, P < 0.05). These results demonstrate an allergen-induced increase in proliferating cells, probably in the BM, and indicate that such cells traffic through the circulation into the lungs in response to allergen inhalation.

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