Both Hematopoietic-Derived and Non–Hematopoietic-Derived β-Arrestin–2 Regulates Murine Allergic Airway Disease

作者：John W. Hollingsworth, Barbara S. Theriot, Zhuowei Li, Barbara L. Lawson, Mary E. Sunday, David A. Schwartz, Julia K. L. Walker · 发表于：American Journal of Respiratory Cell and Molecular Biology · 年份：2009 · DOI：10.1165/rcmb.2009-0198oc · 被引用次数：52 · 研究领域：Receptor Mechanisms and Signaling、Asthma and respiratory diseases、Neuropeptides and Animal Physiology

Allergic asthma, a major cause of morbidity and leading cause of hospitalizations, is an inflammatory disease orchestrated by T helper cells and characterized by the lung migration of eosinophils, which are important asthma effector cells. Lung migration of inflammatory cells requires, among other events, the chemokine receptor transduction of lung-produced inflammatory chemokines. Despite the widespread prevalence of this disease, the molecular mechanisms regulating chemokine production and receptor regulation in asthma are poorly understood. Previous work from our laboratory demonstrated that beta-arrestin-2 positively regulates the development of allergic airway disease in a mouse model, partly through positive regulation of T-lymphocyte chemotaxis to the lung. However, beta-arrestin-2 is expressed in many cell types, including other hematopoietic cells and lung structural cells, which are involved in the development and manifestation of allergic airway disease. To determine the cell types required for beta-arrestin-2-dependent allergic inflammation, we generated bone marrow chimera mice. Using the ovalbumin murine model of allergic airway disease, we show that eosinophilic and lymphocytic inflammation is restored in chimeric mice, with expression of beta-arrestin-2 exclusively on hematopoietic-derived cell types. In contrast, airway hyperresponsiveness is dependent on the expression of beta-arrestin-2 in structural cells. Our data demonstrate that the expression of beta-a...