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Five factors that are problematic are (a) a sustained systemic inflammatory response in the xenograft recipient, (b) thrombotic microangiopathy and disseminated intravascular coagulation, (c) ischemia\u2010reperfusion injury, (d) complement activation, and (e) vascular endothelial cell injury. In xenotransplantation, histones, which are positively charged proteins, are released into the extracellular space from damaged and activated cells, cause cell and tissue damage, and act as danger\/damage\u2010associated molecular patterns (DAMPs) that mediate inflammation, coagulation disorders, an immune response, and cytotoxicity. We have previously demonstrated that serum histones increase after pig\u2010to\u2010baboon organ transplantation and infection. Treatment of the recipient with tocilizumab (interleukin\u20106 receptor blockade) reduces the level of serum histones and C\u2010reactive protein. In this review, the potential role of extracellular histones in xenotransplantation is discussed, and we briefly summarize the relationship between extracellular histones and the inflammatory response, coagulation dysfunction, ischemia\u2010reperfusion injury, the complement system, and vascular endothelial cell injury.<\/jats:p>","DOI":"10.1111\/xen.12618","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T13:52:23Z","timestamp":1600350743000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Extracellular histones and xenotransplantation"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9637-778X","authenticated-orcid":false,"given":"Tao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Organ Transplantation The Second Affiliated Hospital of Hainan Medical University  Haikou Hainan China"},{"name":"The Transplantation Insititute of Hainan Medical University  Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Organ Transplantation The Second Affiliated Hospital of Hainan Medical University  Haikou Hainan China"},{"name":"The Transplantation Insititute of Hainan Medical University  Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houqin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Organ Transplantation The Second Affiliated Hospital of Hainan Medical University  Haikou Hainan China"},{"name":"The Transplantation Insititute of Hainan Medical University  Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8899-9431","authenticated-orcid":false,"given":"David K. 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