Interaction between haemopoietic regulation and airway inflammation.
Asthma is characterized by reversible airway narrowing, by airway hyperresponsiveness, and by airway inflammation. Inhaled allergens are the most important of the stimuli known to cause asthma. Methods for studying inhaled allergen in the laboratory have been well standardized and extensively used for the investigation of the pathophysiology and the pharmacological modulation of allergen-induced airway responses. Allergen inhalation by a sensitized subject results in an early asthmatic response, and, in the majority of subjects, a late asthmatic response and airway hyperresponsiveness. The late response and airway hyperresponsiveness are associated with increases in airway eosinophils and metachromatic cells. Allergen-induced airway inflammation in dogs (predominantly neutrophilic) is associated with increased granulocyte-macrophage progenitors in bone marrow, which is dependent on the effects of a circulating serum factor stimulating the bone marrow. The newly formed cells traffic to the airways. These increases in granulocyte-macrophage progenitors are blocked by inhaled corticosteroids. In human subjects, allergen-induced eosinophilic inflammation is associated with increases in Eo/B progenitors, mediated through up-regulation if the IL-5 receptor on progenitors and increases responsiveness to IL-5. Inhaled corticosteroids also attenuate all allergen-induced physiological responses and airway inflammation, an effect possibly mediated, in part, through inhibition of eosinophil and basophil maturation or release from the bone marrow.
Asthma Research Group and Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
P M
PM
O'Byrne
G M
GM
Gauvreau
L J
LJ
Wood
D000485:Allergens / Q000009:adverse effects; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000503:physiopathology*; D001491:Basophils / Q000502:physiology; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000503:physiopathology*; D004285:Dogs; D004804:Eosinophils / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans
D000485:Allergens