Mesenchymal stem cells enhance NOX2 dependent ROS production and bacterial killing in macrophages during sepsis
Author(s)
Type
Journal Article
Abstract
Human Mesenchymal Stem/Stromal Cells (MSCs) have been reported to produce an M2-like, alternatively activated phenotype in macrophages. In addition, MSCs mediate effective bacterial clearance in pre-clinical sepsis models. Thus, MSCs have a paradoxical anti-microbial and anti-inflammatory response that is not understood. Here we studied the phenotypic and functional response of monocyte-derived human macrophages to MSC exposure in vitroMSCs induced two distinct, co-existent phenotypes: M2-like macrophages (generally elongated morphology, CD163 positive, acute phagosomal acidification, low NADPH oxidase expression and low phagosomal superoxide production) and M1-like macrophages, characterised by high levels of phagosomal superoxide production. Enhanced phagosomal ROS production was also observed in alveolar macrophages from a rodent model of pneumonia-induced sepsis. The production of M1-like macrophages was dependent on PGE2 and PI3 kinase. MSCs enhanced human macrophage phagocytosis of unopsonized bacteria and enhanced bacterial killing compared to untreated macrophages. Bacterial killing was significantly reduced by blockade of NOX2 using diphenyleneiodonium, suggesting that M1-like cells are primarily responsible for this effect. MSCs also enhanced phagocytosis and polarisation of M1-like macrophages derived from patients with severe sepsis.The enhanced anti-microbial capacity (M1-like), and inflammation resolving phenotype (M2-like), may account for the paradoxical effect of these cells in sepsis in vivo.
Date Issued
2018-04-26
Date Acceptance
2018-03-01
Citation
European Respiratory Journal, 2018, 51 (4)
ISSN
0903-1936
Publisher
European Respiratory Society
Journal / Book Title
European Respiratory Journal
Volume
51
Issue
4
Copyright Statement
© ERS 2018. This is an author-submitted, peer-reviewed version of a manuscript that has been accepted for publication in the European Respiratory Journal, prior to copy-editing, formatting and typesetting. This version of the manuscript may not be duplicated or reproduced without prior permission from the copyright owner, the European Respiratory Society. The publisher is not responsible or liable for any errors or omissions in this version of the manuscript or in any version derived from it by any other parties. The final, copy-edited, published article, which is the version of record, is available without a subscription 18 months after the date of issue publication.
Sponsor
The Academy of Medical Sciences
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29519920
PII: 13993003.02021-2017
Grant Number
n/a
Subjects
Science & Technology
Life Sciences & Biomedicine
Respiratory System
STROMAL CELLS
LUNG INJURY
PROSTAGLANDIN E-2
BONE-MARROW
MITOCHONDRIAL TRANSFER
ACTIVATED MACROPHAGES
PULMONARY INFECTION
STEM/STROMAL CELLS
IMMUNE-RESPONSES
REDUCE MORTALITY
11 Medical And Health Sciences
Publication Status
Published
Coverage Spatial
England
Article Number
1702021
Date Publish Online
2018-03-08