title: A2B adenosine receptor expression by myeloid cells is proinflammatory in murine allergic-airway inflammation.
abstract: Asthma is a chronic condition with high morbidity and healthcare costs, and cockroach allergens are an established cause of urban pediatric asthma. A better understanding of cell types involved in promoting lung inflammation could provide new targets for the treatment of chronic pulmonary disease. Because of its role in regulating myeloid cell-dependent inflammatory processes, we examined A(2B) R expression by myeloid cells in a cockroach allergen model of murine asthma-like pulmonary inflammation. Both systemic and myeloid tissue-specific A(2B) R deletion significantly decreased pulmonary inflammatory cell recruitment, airway mucin production, and proinflammatory cytokine secretion after final allergen challenge in sensitized mice. A(2B) R deficiency resulted in a dramatic reduction on Th2-type airways responses with decreased pulmonary eosinophilia without augmenting neutrophilia, and decreased lung IL-4, IL-5, and IL-13 production. Chemokine analysis demonstrated that eotaxin 1 and 2 secretion in response to repeated allergen challenge is myeloid cell A(2B) R dependent. In contrast, there were no differences in the levels of the CXC chemokines keratinocyte-derived chemokine and MIP-2 in the myeloid cell A(2B) R-deficient mice, strengthening A(2B) R involvement in the development of Th2-type airways inflammation. Proinflammatory TNF-α, IFN-γ, and IL-17 secretion were also reduced in systemic and myeloid tissue-specific A(2B) R deletion mouse lines. Our results demonstrate Th2-type predominance for A(2B) R expression by myeloid cells as a mechanism of development of asthma-like pulmonary inflammation.
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Bryan G
authors.initials: BG
authors.lastname: Belikoff
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Vaickus
authors.forename: Michail
authors.initials: M
authors.lastname: Sitkovsky
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Remick
mesh_terms: D000485:Allergens / Q000633:toxicity*; D000818:Animals; D020048:Blattellidae / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000502:physiology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D043704:Receptor, Adenosine A2B / Q000008:administration & dosage* / Q000172:deficiency / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
chemical_list: D000485:Allergens; D018836:Inflammation Mediators; D043704:Receptor, Adenosine A2B