The Regulation of Neutrophil Extracellular Trap–induced Tissue Damage by Human CD177

• Main Authors: Tomohisa Yoneyama, MD, Akira Maeda, MD, PhD, Shuhei Kogata, MD, Chiyoshi Toyama, MD, Pei-Chi Lo, PhD, Kazunori Masahata, MD, PhD, Masafumi Kamiyama, MD, PhD, Tomoko Haneda, MS, Chizu Okamatu, BS, Hiroshi Eguchi, MD, PhD, Yuko Tazuke, MD, PhD, Takehisa Ueno, MD, PhD, Hiroomi Okuyama, MD, PhD, Shuji Miyagawa, MD, PhD
• Format: Article
• Language: English
• Published: Wolters Kluwer 2021-08-01
• Series: Transplantation Direct
• Online Access: http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001175

Background. Neutrophil-induced tissue damage contributes to the rejection in xenotransplantation. Therefore, suppressing neutrophil function could be effective in suppressing xenogeneic rejection. In a previous study, we demonstrated that the ectopic expression of human cluster of differentiation 31 (CD31) on porcine endothelial cells (PEC) significantly suppressed neutrophil-mediated cytotoxicity through the homophilic binding of CD31. Cluster of differentiation 177 (CD177) was recently reported to be a high-affinity heterophilic binding partner for CD31 on endothelial cells. Thus, we hypothesized that human CD177 on PEC might induce a stronger suppression in neutrophil-mediated cytotoxicity compared with CD31. In this study, the inhibitory function of human CD177 on PEC in neutrophil-mediated cytotoxicity was investigated. Methods. PEC were transfected with a cloning plasmid containing cDNA inserts that encoded for hCD177 and hCD31 genes. Neutrophil-induced cytotoxicity was evaluated by flow cytometry after coculturing with PEC or PEC/CD177 in the presence of phorbol 12-myristate 13-acetate. To elucidate the mechanisms responsible for hCD177-induced suppression, the phosphorylation of src homology region 2 domain containing phosphatase 1 was measured by immunoblot analysis. Results. Human CD177 on PEC induced a significant reduction in neutrophil-induced cytotoxicity. In addition, CD177 on PEC induced a significant increase in the phosphorylation of src homology region 2 domain-containing phosphatase 1 in neutrophils and suppressed NETosis. Conclusions. These findings suggest that human CD177 suppresses neutrophil-mediated cytotoxicity through the inhibition of NETosis.