Both hematopoietic-derived and non-hematopoietic-derived {beta}-arrestin-2 regulates murine allergic airway disease.
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-arrestin-2 in at least two divergent cell types contributes to the pathogenesis of allergic airway disease.
Hollingsworth
John W
JW
Duke University Medical Center, Durham, NC 27710, USA.
Theriot
Barbara S
BS
Li
Zhouwei
Z
Lawson
Barbara L
BL
Sunday
Mary
M
Schwartz
David A
DA
Walker
Julia K L
JK
D019264:Adoptive Transfer; D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D001249:Asthma / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism; D016026:Bone Marrow Transplantation; D004804:Eosinophils / Q000378:metabolism*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D018793:Interleukin-13 / Q000494:pharmacology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000502:physiology; D012137:Respiratory System / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
C000605258:Arrb2 protein, mouse; D019390:Arrestins; D018793:Interleukin-13; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D010047:Ovalbumin