The bone marrow and airway inflammation: evidence for allergy as a systemic disease
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SummaryRhinitis and asthma are linked closely epidemiologically, as has been known for quite some time and emphasized in recent surveys (ISAAC study). Patients with seasonal allergic rhinitis without asthma symptoms can, as a group, be shown to have increased bronchial hyperresponsiveness. During the course of seasonal allergen exposure, patients with allergic rhinitis can be shown to have increased numbers of inflammatory cells (eosinophils and mast cells) in the lower airways, even without symptoms of lower airway disease. Long‐standing observations from our laboratory have indicated fluctuations of eosinophil/basophil (Eo‐B) progenitors in the peripheral blood in patients with seasonal allergic rhinitis, paralleling changes that are recognized in mature eosinophils and basophils in circulation. The finding of Eo‐B progenitor decreases during the height of seasonal allergen exposure led us to hypothesize the concept of ‘in situ haemopoiesis’ to explain a process of systemic activation of haemopoietic mechanisms, in which communication among bone marrow peripheral blood and airway tissue compartments contributed to the allergic inflammatory process at a systemic level. Indeed, allergen challenge to the lower airways in atopic asthmatics elicits an immediate rise in Eo‐B progenitors, especially in subjects with late phase responses. These original observations have been buttressed by a series of investigations demonstrating conclusively that exacerbations of asthma are attended by increases in peripheral blood Eo‐B progenitors; that allergen challenge to dogs or mice with allergic airways inflammation elicits bone marrow progenitor responses, with trafficking of bone marrow cells to the airway either in pure upper or lower airway disease; and that allergen challenge to atopic asthmatics up‐regulates the high affinity receptor for IL‐5 on bone marrow progenitors (IL‐5Rα), beginning a process of eosinophil differentiation that is probably driven by the release of a serum haemopoietic factor – as we have found in the canine model – which acts on the bone marrow and initiates a series of systemic events.
