Platelets are necessary for airway wall remodeling in a murine model of chronic allergic inflammation.
Asthma is associated with airway remodeling. Evidence of platelet recruitment to the lungs of asthmatics after allergen exposure suggests platelets participate in various aspects of asthma; although their importance is unknown in the context of airway remodeling, their involvement in atherosclerosis is established. Studies from our laboratory have shown a requirement for platelets in pulmonary leukocyte recruitment in a murine model of allergic lung inflammation. Presently, the effects of platelet depletion and corticosteroid administration on airway remodeling and lung function were examined. Ovalbumin (OVA)-sensitized mice, exposed to aerosolized OVA for 8 weeks, demonstrated epithelial and smooth muscle thickening, and subepithelial reticular fiber deposition in the distal airways. The depletion of platelets via an immunologic (antiplatelet antisera) or nonimmunologic (busulfan) method, markedly reduced airway remodeling. In contrast, dexamethasone administration did not affect epithelial thickening or subepithelial fibrosis, despite significantly inhibiting leukocyte recruitment. Thus, pathways leading to certain aspects of airway remodeling may not depend on leukocyte recruitment, whereas platelet activation is obligatory. OVA-sensitized mice exhibited airway hyperresponsiveness (AHR) compared with sham-sensitized mice following chronic OVA exposure. Neither platelet depletion nor dexamethasone administration inhibited chronic AHR; thus, mechanisms other than inflammation and airway remodeling may be involved in the pathogenesis of chronic AHR.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001792:Blood Platelets / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010976:Platelet Count; D011652:Pulmonary Circulation / Q000276:immunology / Q000502:physiology; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D013921:Thrombocytopenia / Q000276:immunology
D000305:Adrenal Cortex Hormones; D007073:Immunoglobulin E; D003907:Dexamethasone; D010047:Ovalbumin