Identification of Siglec-1-negative alveolar macrophages with pro-inflammatory phenotypes in chronic obstructive pulmonary disease
Am J Physiol Lung Cell Mol Physiol. 2024 Mar 26. doi: 10.1152/ajplung.00303.2023. Online ahead of print.ABSTRACTAlveolar macrophages (AMs) in patients with chronic obstructive pulmonary disease (COPD) orchestrate persistent inflammation in the airway. However, sub-populations of AMs participating in the 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 pro-inflammatory phenotype and is 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+SSChiFSChi, Siglec-1-SSChiFSChi and Siglec-1-SSCloFSClo subsets. The Siglec-1-SSCloFSClo subset number was increased in COPD. RNA-sequencing revealed upregulation of multiple pro-inflammatory signaling pathways and emphysema-associated matrix metalloproteases in the Siglec-1-SSCloFSClo subset. Gene set enrichment analysis indicated that the Siglec-1-SSCloFSClo 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 associ...
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Takuya Saito Naoya Fujino Yorihiko Kyogoku Mitsuhiro Yamada Koji Okutomo Yoshinao Ono Shuichi Konno Takuto Endo Koji Itakura Shuichiro Matsumoto Hirohito Sano Hiroyuki Aizawa Tadahisa Numakura Katsuhiro Onodera Yoshinori Okada Tracy Hussell Masakazu Ichin Source Type: research