Macrophages with reduced expressions of classical M1 and M2 surface markers in human bronchoalveolar lavage fluid exhibit pro-inflammatory gene signatures

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:11

Enthalten in:

Scientific reports - 11(2021), 1 vom: 15. Apr., Seite 8282

Sprache:

Englisch

Beteiligte Personen:

Takiguchi, Hiroto [VerfasserIn]
Yang, Chen X [VerfasserIn]
Yang, Cheng Wei Tony [VerfasserIn]
Sahin, Basak [VerfasserIn]
Whalen, Beth A [VerfasserIn]
Milne, Stephen [VerfasserIn]
Akata, Kentaro [VerfasserIn]
Yamasaki, Kei [VerfasserIn]
Yang, Julia Shun Wei [VerfasserIn]
Cheung, Chung Yan [VerfasserIn]
Vander Werff, Ryan [VerfasserIn]
McNagny, Kelly M [VerfasserIn]
Leitao Filho, Fernando Sergio [VerfasserIn]
Shaipanich, Tawimas [VerfasserIn]
van Eeden, Stephan F [VerfasserIn]
Obeidat, Ma'en [VerfasserIn]
Leung, Janice M [VerfasserIn]
Sin, Don D [VerfasserIn]

Links:

Volltext

Themen:

Antigens, CD
Antigens, Differentiation, Myelomonocytic
Antigens, Surface
CD163 antigen
CD40 Antigens
Journal Article
Receptors, Cell Surface
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 15.11.2021

Date Revised 15.11.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41598-021-87720-y

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM324140290