TY - JOUR T1 - Mesenchymal stem cells enhance NOX2-dependent reactive oxygen species production and bacterial killing in macrophages during sepsis JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.02021-2017 VL - 51 IS - 4 SP - 1702021 AU - Razieh Rabani AU - Allen Volchuk AU - Mirjana Jerkic AU - Lindsay Ormesher AU - Linda Garces-Ramirez AU - Johnathan Canton AU - Claire Masterson AU - Stephane Gagnon AU - Kate C. Tatham AU - John Marshall AU - Sergio Grinstein AU - John G. Laffey AU - Katalin Szaszi AU - Gerard F. Curley Y1 - 2018/04/01 UR - http://erj.ersjournals.com/content/51/4/1702021.abstract N2 - 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 antimicrobial 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 vitro.MSCs induced two distinct, coexistent phenotypes: M2-like macrophages (generally elongated morphology, CD163+, acute phagosomal acidification, low NOX2 expression and limited phagosomal superoxide production) and M1-like macrophages characterised by high levels of phagosomal superoxide production. Enhanced phagosomal reactive oxygen species production was also observed in alveolar macrophages from a rodent model of pneumonia-induced sepsis. The production of M1-like macrophages was dependent on prostaglandin E2 and phosphatidylinositol 3-kinase. MSCs enhanced human macrophage phagocytosis of unopsonised bacteria and enhanced bacterial killing compared with 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 antimicrobial capacity (M1-like) and inflammation resolving phenotype (M2-like) may account for the paradoxical effect of these cells in sepsis in vivo.Mesenchymal stem cells enhance bacterial killing via production of phagosomal reactive oxygen species in macrophages http://ow.ly/tigl30iGFPG ER -