Procollagen C‐Endopeptidase Enhancer 2 Secreted by Tonsil‐Derived Mesenchymal Stem Cells Increases the Oxidative Burst of Promyelocytic HL‐60 Cells

Reactive oxygen species (ROS) generated by neutrophils provide a frontline defence against invading pathogens. We investigated the supportive effect of tonsil‐derived mesenchymal stem cells (TMSCs) on ROS generation from neutrophils using promyelocytic HL‐60 cells. Methods: Differentiated HL‐60 (dHL‐60) cells were cocultured with TMSCs isolated from 25 independent donors, and ROS generation in dHL‐60 cells was measured using luminescence. RNA sequencing and real‐time PCR were performed to identify the candidate genes of TMSCs involved in augmenting the oxidative burst of dHL‐60 cells. Transcriptome analysis of TMSCs derived from 25 independent donors revealed high levels of procollagen C‐endopeptidase enhancer 2 (PCOLCE2) in TMSCs, which were highly effective in potentiating ROS generation in dHL‐60 cells. In addition, PCOLCE2 knockdown in TMSCs abrogated TMSC‐induced enhancement of ROS production in dHL‐60 cells, indicating that TMSCs increased the oxidative burst in dHL‐60 cells via PCOLCE2. Furthermore, the direct addition of recombinant PCOLCE2 protein increased ROS production in dHL‐60 cells. These results suggest that PCOLCE2 secreted by TMSCs may be used as a therapeutic candidate to enhance host defences by increasing neutrophil oxidative bursts. PCOLCE2 levels in TMSCs could be used as a marker to select TMSCs exhibiting high efficacy for enhancing neutrophil oxidative bursts.