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: Bryan G Belikoff, Louis J Vaickus, Michail Sitkovsky, Daniel G Remick
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 189 Issue 7 Pg. 3707-13 (Oct 01 2012) ISSN: 1550-6606 [Electronic] United States
• PMID: 22956582 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Allergens
• Inflammation Mediators
• Receptor, Adenosine A2B

Topics

• Allergens (toxicity)
• Animals
• Blattellidae (immunology)
• Chronic Disease
• Female
• Inflammation (immunology, metabolism, pathology)
• Inflammation Mediators (administration & dosage, physiology)
• Lung (immunology, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Myeloid Cells (immunology, metabolism, pathology)
• Receptor, Adenosine A2B (administration & dosage, deficiency, physiology)
• Respiratory Hypersensitivity (immunology, metabolism, pathology)