ALLERGEN CHALLENGE INCREASES CELL TRAFFIC BETWEEN BONE-MARROW AND LUNG

Increases in inflammatory-cell progenitors have been demonstrated in t he bone marrow (BM) after inhalation of Ascaris suum in dogs at the ti me of allergen-induced airway hyperresponsiveness (AHR). The aim of th is study was to evaluate the effect of allergen challenge on trafficki ng of inflammatory cells and their progenitors from the BM to the lung , using a marker of proliferating cells, bromodeoxyuridine (BrdU). Brd U is a thymidine analogue taken up by the DNA of dividing cells, and c an 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 th e 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 lavag e (BAL) samples were taken 24 h after challenge. BrdU-positive cells w ere detected in cytospin preparations of these samples, using IHC. All ergen inhalation caused AHR (P < 0.05) at 24 h after allergen challeng er 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% aft er diluent (P < 0.005); in EM 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 ch allenge and 0.8 +/- 0.3% after diluent (P < 0.005). There was a signif icant correlation between the number of BAL neutrophils and the percen tage of BrdU-positive BAL cells (r(2) = 0.54, P < 0.05). These results demonstrate an allergen-induced increase in proliferating cells, prob ably in the BM, and indicate that such cells traffic through the circu lation into the lungs in response to allergen inhalation.