International Immunology Advance Access published online on October 29, 2007
International Immunology, doi:10.1093/intimm/dxm108
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Allergen-induced CD11b+ CD11cint CCR3+ macrophages in the lung promote eosinophilic airway inflammation in a mouse asthma model
1 Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
2 Division of Allergy, University of Ulsan College of Medicine, Seoul, Republic of Korea
Correspondence to: Correspondence to: Ki-Young Lee; E-mail: thylee{at}med.skku.ac.kr
Although the recruitment of macrophages to the lung is a central feature of airway inflammation, its function in ongoing Th2 cell-mediated eosinophilic airway inflammation remains controversial. Here, we have demonstrated that the allergen-induced CD11b+ CD11cint macrophage expressing CC chemokine receptor 3 (CCR3) in the lung performs a crucial function in the induction of eosinophilic asthma in a murine model. In the lungs of normal mice, residential cells evidencing high granularity phenotypically evidenced CD11bint CD11c+ or CD11b+ CD11cint cells, appearing at a 2:1 ratio. After allergen challenge, however, this reverses dramatically, up to a ratio of one to six. Approximately 91% of increased CD11b+ CD11cint cells evidenced the expression of the CCR3 eotaxin receptor, but not other chemokine receptors, such as CCR5 and CXCR4. Interestingly, the CD11b+ CD11cint cells purified from the lungs of OVA (ovalbumin)-sensitized and challenged mice evidenced higher antigen-presenting activity than was observed in CD11bint CD11c+ cells. In order to investigate the in vivo function of CD11b+ CD11cint cells, the cells were isolated from the lungs of OVA-sensitized and challenged mice and then adoptively transferred prior to the allergen challenge of normal mice. In the CD11b+ CD11cint-transferred mice airway hyperresponsiveness, eosinophilic inflammation in the lung and Th2 cytokine secretion in the bronchoalveolar lavage fluids were significantly enhanced as the result of OVA challenge, as compared with the mice that received OVA-primed CD90+ T cells or CD11bint CD11c+ cells. These findings show that CD11b+ CD11cint macrophages expressing CCR3 as key pro-inflammatory cells are both necessary and sufficient for allergen-specific T cell stimulation during ongoing eosinophilic airway inflammation.
Keywords: adoptive transfer, allergic asthma, lung, macrophage, Th2 cytokines
* These authors contributed equally to this study
Transmitting editor: K. Okumura
Received 11 April 2007, accepted 28 September 2007.