Explaining the polarized macrophage pool during murine allergic lung inflammation.
Christina Draijer, Laura Florez-Sampedro, Catharina Reker-Smit, Eduard Post, Fransien van Dijk, Barbro N Melgert
Author Information
Christina Draijer: GRIAC- Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Laura Florez-Sampedro: GRIAC- Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Catharina Reker-Smit: Department of Pharmacokinetics, Toxicology and Targeting, University of Groningen, Groningen, Netherlands.
Eduard Post: Department of Pharmacokinetics, Toxicology and Targeting, University of Groningen, Groningen, Netherlands.
Fransien van Dijk: GRIAC- Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Barbro N Melgert: GRIAC- Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Introduction: Differentially polarized macrophages, especially YM1+ and MHCII+ macrophages, play an important role in asthma development. The origin of these polarized macrophages has not been elucidated yet. We therefore aimed to investigate how proliferation, monocyte recruitment, and/or switching of polarization states contribute to this specific pool of polarized interstitial and alveolar macrophages during development of house dust mite (HDM)-induced allergiclung inflammation in mice. Methods: Male and female mice were first treated intranasally with PKH26 to label lung-resident macrophages and were then exposed to either HDM or phosphate-buffered saline (PBS) for two weeks. Different myeloid immune cell types were quantified in lung tissue and blood using flow cytometry. Results: We found that macrophage polarization only starts up in the second week of HDM exposures. Before this happened, unpolarized alveolar and interstitial macrophages transiently increased in HDM-exposed mice. This transient increase was mostly local proliferation of alveolar macrophages, while interstitial macrophages also contained unlabeled macrophages suggesting monocyte contribution. After two weeks of exposures, the number of interstitial and alveolar macrophages was similar between HDM and PBS-exposed mice, but the distribution of polarization states was remarkably different. HDM-exposed mice selectively developed YM1+ alveolar macrophages and MHCII-hi interstitial macrophages while nonpolarized macrophages were lost compared to PBS-exposed mice. Discussion: In this HDM model we have shown that development of a polarized macrophage pool during allergic inflammation is first dependent on proliferation of nonpolarized tissue-resident macrophages with some help of infiltrating unlabeled cells, presumably circulating monocytes. These nonpolarized macrophages then acquire their polarized phenotype by upregulating YM1 on alveolar macrophages and MHCII on interstitial macrophages. This novel information will help us to better understand the role of macrophages in asthma and designing therapeutic strategies targeting macrophage functions.
