학술논문
Identification of Siglec-1-negative alveolar macrophages with proinflammatory phenotypes in chronic obstructive pulmonary disease.
Document Type
Academic Journal
Author
Saito T; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Fujino N; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Kyogoku Y; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Yamada M; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Okutomo K; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Ono Y; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Konno S; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Endo T; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Itakura K; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Matsumoto S; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Sano H; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Aizawa H; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Numakura T; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Onodera K; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Okada Y; Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.; Hussell T; Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, United Kingdom.; Ichinose M; Academic Center, Osaki Citizen Hospital, Miyagi, Japan.; Sugiura H; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Source
Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901229 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1504 (Electronic) Linking ISSN: 10400605 NLM ISO Abbreviation: Am J Physiol Lung Cell Mol Physiol Subsets: MEDLINE
Subject
Language
English
Abstract
Alveolar macrophages (AMs) in patients with chronic obstructive pulmonary disease (COPD) orchestrate persistent inflammation in the airway. However, subpopulations of AMs participating in chronic inflammation have been poorly characterized. We previously reported that Siglec-1 expression on AMs, which is important for bacteria engulfment, was decreased in COPD. Here, we show that Siglec-1-negative AMs isolated from COPD lung tissues exhibit a proinflammatory phenotype and are associated with poor clinical outcomes in patients with COPD. Using flow cytometry, we segregated three subsets of AMs based on the expression of Siglec-1 and their side scattergram (SSC) and forward scattergram (FSC) properties: Siglec-1 + SSC hi FSC hi , Siglec-1 - SSC hi FSC hi , and Siglec-1 - SSC lo FSC lo subsets. The Siglec-1 - SSC lo FSC lo subset number was increased in COPD. RNA sequencing revealed upregulation of multiple proinflammatory signaling pathways and emphysema-associated matrix metalloproteases in the Siglec-1 - SSC lo FSC lo subset. Gene set enrichment analysis indicated that the Siglec-1 - SSC lo FSC lo subset adopted intermediate phenotypes between monocytes and mature alveolar macrophages. Functionally, these cells produced TNF-α, IL-6, and IL-8 at baseline, and these cytokines were significantly increased in response to viral RNA. The increase in Siglec-1-negative AMs in induced sputum is associated with future exacerbation risk and lung function decline in patients with COPD. Collectively, the novel Siglec-1 - SSC lo FSC lo subset of AMs displays proinflammatory properties, and their emergence in COPD airways may be associated with poor clinical outcomes. NEW & NOTEWORTHY Alveolar macrophages (AMs) in patients with chronic obstructive pulmonary disease (COPD) orchestrate persistent inflammation in the airway. We find that Siglec-1-negative alveolar macrophages have a wide range of proinflammatory landscapes and a protease-expressing phenotype. Moreover, this subset is associated with the pathogenesis of COPD and responds to viral stimuli.