Platelets are necessary for airway wall remodeling in a murine model of chronic allergic inflammation
Platelets are necessary for airway wall remodeling in a murine model of chronic allergic inflammation
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DOI：
10.1182/blood-2003-05-1707
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发表时间：
2004-01-15
期刊：
影响因子：
20.3
通讯作者：
Page, CP
中科院分区：
文献类型：
--
作者：
Pitchford, SC;Riffo-Vasquez, Y;Page, CP
哮喘与气道重塑有关。暴露于过敏原后，哮喘患者肺部的血小板募集证据表明，血小板参与哮喘的各个方面；虽然它们在气道重塑中的重要性尚不清楚，但它们与动脉粥样硬化的关系是确定的。我们实验室的研究表明，在过敏性肺部炎症的小鼠模型中，肺白细胞募集需要血小板。目前，研究了血小板消耗和皮质类固醇给药对气道重塑和肺功能的影响。卵清蛋白（OVA）致敏小鼠，暴露于雾化OVA 8周后，显示上皮和平滑肌增厚，上皮下网状纤维沉积在远端气道。通过免疫（抗血小板抗血清）或非免疫（busulfan）方法消耗血小板，显著减少气道重塑。相反，地塞米松给药不影响上皮增厚或上皮下纤维化，尽管明显抑制白细胞募集。因此，导致气道重塑某些方面的途径可能不依赖于白细胞募集，而血小板激活是强制性的。与假致敏小鼠相比，OVA致敏小鼠在慢性OVA暴露后表现出气道高反应性（AHR）。血小板消耗和地塞米松均未抑制慢性AHR；因此，慢性AHR的发病机制可能涉及炎症和气道重塑以外的机制。
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.