Changes in Bone Marrow Inflammatory Cell Progenitors after Inhaled Allergen in Asthmatic Subjects

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Abstract
Increases in inflammatory cell progenitors, particularly eosinophil/basophil colony-forming cells (Eo/ B-CFU), occur in peripheral blood after allergen provocation. The role of bone marrow (BM) in these reactions is unclear. We examined the effect of allergen challenge on human bone marrow progeni- tor cell growth. Fifteen asthmatic subjects, eight dual responders (DR) and seven isolated early re- sponders (IER), were challenged with inhaled allergen. BM aspirates were taken before and 24 h after challenge and progenitors were enumerated by a colony-forming assay. Eo/B-CFU numbers increased in both groups after allergen challenge (p , 0.0001). For DR, the increases were significant for BM in- cubated with optimal GMCSF and IL-5, but not with IL-3. For IER, the increases were significant for all three cytokines tested. At a suboptimal concentration of IL-5, there was a significant increase in the number of Eo/B-CFU after allergen in the DR, from 5.25 6 1.2 to 9.68 6 2.1 per 2.5 3 10 5 cells plated (p , 0.01), which was not demonstrated in the IER (p 5 0.94). The responses at this concentration of IL-5 were different between groups (p , 0.05). These results demonstrate that inhaled allergen in- creases BM Eo/B-CFU, and that the bone marrow of dual responders is more responsive to IL-5 after allergen. Wood LJ, Inman MD, Watson RM, Foley R, Denburg JA, O'Byrne PM. Changes in bone marrow inflammatory cell progenitors after inhaled allergen in asthmatic subjects. AM J RESPIR CRIT CARE MED 1998;157:99-105. Asthma is a disease characterized by bronchoconstriction, air- way hyperresponsiveness, and airway inflammation. Inhala- tion of allergen by sensitized subjects is an important cause of asthma, and is characterized by biphasic responses known as the early- and late-phase asthmatic responses. Late asthmatic responses (LAR) are associated with transient increases in airway hyperresponsiveness (1), usually lasting several days, and increases in the numbers of activated eosinophils and metachromatic cells in the airways (2); however, subjects de- veloping isolated early asthmatic responses also develop air- way hyperresponsiveness, but to a much lesser extent than those patients developing late responses (3). The predominant cell infiltrating the airways during the late response is the eosinophil. These cells are selectively in- creased in sputum (4) and bronchoalveolar lavage fluid