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Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2

DOI: 10.1186/1465-9921-5-12

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Abstract:

To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response.We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines.We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2.Monocyte chemoattractant protein-1 (MCP-1, also known as CCL2) and its receptor, CCR2, have been the focus of intense interest due to increasing awareness of their association with debilitating human diseases, including asthma [1-3] and pulmonary fibrosis [4-7]. Since MCP-1 attracts and activates a variety of cells, including monocytes, immature dendritic cells, basophils, natural killer cells, and a subset of T lymphocytes [8-17], MCP-1 may have multiple roles in the immune response. Models of Th1 or Th2 inflammation applied to mice deficient in either MCP-1 or CCR2 have clearly shown important roles for this chemokine and its receptor in the development of inflammation [18-24]. However, results obtained using allergen-induced models of asthma (ovalbumin and cockroach antigen) in CCR2-deficient mice are varied, showing either increased, decreased or unchanged Th2 inflammation and airway hyperreactivity (AHR) [25-27], possibly due to differences in

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