Macrophages with reduced expressions of classical M1 and M2 surface markers in human bronchoalveolar lavage fluid exhibit pro-inflammatory gene signatures
Abstract The classical M1/M2 polarity of macrophages may not be applicable to inflammatory lung diseases including chronic obstructive pulmonary disease (COPD) due to the complex microenvironment in lungs and the plasticity of macrophages. We examined macrophage sub-phenotypes in bronchoalveolar lav...
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Nature Portfolio
2021
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oai:doaj.org-article:052ad98032564138a6298f7a605c7d0d2021-12-02T14:27:56ZMacrophages with reduced expressions of classical M1 and M2 surface markers in human bronchoalveolar lavage fluid exhibit pro-inflammatory gene signatures10.1038/s41598-021-87720-y2045-2322https://doaj.org/article/052ad98032564138a6298f7a605c7d0d2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87720-yhttps://doaj.org/toc/2045-2322Abstract The classical M1/M2 polarity of macrophages may not be applicable to inflammatory lung diseases including chronic obstructive pulmonary disease (COPD) due to the complex microenvironment in lungs and the plasticity of macrophages. We examined macrophage sub-phenotypes in bronchoalveolar lavage (BAL) fluid in 25 participants with CD40 (a M1 marker) and CD163 (a M2 marker). Of these, we performed RNA-sequencing on each subtype in 10 patients using the Illumina NextSeq 500. Approximately 25% of the macrophages did not harbor classical M1 or M2 surface markers (double negative, DN), and these cells were significantly enriched in COPD patients compared with non-COPD patients (46.7% vs. 14.5%, p < 0.001). 1886 genes were differentially expressed in the DN subtype compared with all other subtypes at a 10% false discovery rate. The 602 up-regulated genes included 15 mitochondrial genes and were enriched in 86 gene ontology (GO) biological processes including inflammatory responses. Modules associated with cellular functions including oxidative phosphorylation were significantly down-regulated in the DN subtype. Macrophages in the human BAL fluid, which were negative for both M1/M2 surface markers, harbored a gene signature that was pro-inflammatory and suggested dysfunction in cellular homeostasis. These macrophages may contribute to the pathogenesis and manifestations of inflammatory lung diseases such as COPD.Hiroto TakiguchiChen X. YangCheng Wei Tony YangBasak SahinBeth A. WhalenStephen MilneKentaro AkataKei YamasakiJulia Shun Wei YangChung Yan CheungRyan Vander WerffKelly M. McNagnyFernando Sergio Leitao FilhoTawimas ShaipanichStephan F. van EedenMa’en ObeidatJanice M. LeungDon D. SinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
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Medicine R Science Q Hiroto Takiguchi Chen X. Yang Cheng Wei Tony Yang Basak Sahin Beth A. Whalen Stephen Milne Kentaro Akata Kei Yamasaki Julia Shun Wei Yang Chung Yan Cheung Ryan Vander Werff Kelly M. McNagny Fernando Sergio Leitao Filho Tawimas Shaipanich Stephan F. van Eeden Ma’en Obeidat Janice M. Leung Don D. Sin Macrophages with reduced expressions of classical M1 and M2 surface markers in human bronchoalveolar lavage fluid exhibit pro-inflammatory gene signatures |
| description |
Abstract The classical M1/M2 polarity of macrophages may not be applicable to inflammatory lung diseases including chronic obstructive pulmonary disease (COPD) due to the complex microenvironment in lungs and the plasticity of macrophages. We examined macrophage sub-phenotypes in bronchoalveolar lavage (BAL) fluid in 25 participants with CD40 (a M1 marker) and CD163 (a M2 marker). Of these, we performed RNA-sequencing on each subtype in 10 patients using the Illumina NextSeq 500. Approximately 25% of the macrophages did not harbor classical M1 or M2 surface markers (double negative, DN), and these cells were significantly enriched in COPD patients compared with non-COPD patients (46.7% vs. 14.5%, p < 0.001). 1886 genes were differentially expressed in the DN subtype compared with all other subtypes at a 10% false discovery rate. The 602 up-regulated genes included 15 mitochondrial genes and were enriched in 86 gene ontology (GO) biological processes including inflammatory responses. Modules associated with cellular functions including oxidative phosphorylation were significantly down-regulated in the DN subtype. Macrophages in the human BAL fluid, which were negative for both M1/M2 surface markers, harbored a gene signature that was pro-inflammatory and suggested dysfunction in cellular homeostasis. These macrophages may contribute to the pathogenesis and manifestations of inflammatory lung diseases such as COPD. |
| format |
article |
| author |
Hiroto Takiguchi Chen X. Yang Cheng Wei Tony Yang Basak Sahin Beth A. Whalen Stephen Milne Kentaro Akata Kei Yamasaki Julia Shun Wei Yang Chung Yan Cheung Ryan Vander Werff Kelly M. McNagny Fernando Sergio Leitao Filho Tawimas Shaipanich Stephan F. van Eeden Ma’en Obeidat Janice M. Leung Don D. Sin |
| author_facet |
Hiroto Takiguchi Chen X. Yang Cheng Wei Tony Yang Basak Sahin Beth A. Whalen Stephen Milne Kentaro Akata Kei Yamasaki Julia Shun Wei Yang Chung Yan Cheung Ryan Vander Werff Kelly M. McNagny Fernando Sergio Leitao Filho Tawimas Shaipanich Stephan F. van Eeden Ma’en Obeidat Janice M. Leung Don D. Sin |
| author_sort |
Hiroto Takiguchi |
| title |
Macrophages with reduced expressions of classical M1 and M2 surface markers in human bronchoalveolar lavage fluid exhibit pro-inflammatory gene signatures |
| title_short |
Macrophages with reduced expressions of classical M1 and M2 surface markers in human bronchoalveolar lavage fluid exhibit pro-inflammatory gene signatures |
| title_full |
Macrophages with reduced expressions of classical M1 and M2 surface markers in human bronchoalveolar lavage fluid exhibit pro-inflammatory gene signatures |
| title_fullStr |
Macrophages with reduced expressions of classical M1 and M2 surface markers in human bronchoalveolar lavage fluid exhibit pro-inflammatory gene signatures |
| title_full_unstemmed |
Macrophages with reduced expressions of classical M1 and M2 surface markers in human bronchoalveolar lavage fluid exhibit pro-inflammatory gene signatures |
| title_sort |
macrophages with reduced expressions of classical m1 and m2 surface markers in human bronchoalveolar lavage fluid exhibit pro-inflammatory gene signatures |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/052ad98032564138a6298f7a605c7d0d |
| work_keys_str_mv |
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