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However, our understanding of the immense complexity of its interaction with other constituents of the innate immune response and of the coagulation, adaptive immune, and inflammatory responses to a xenograft is steadily increasing. In addition, the complement system plays a function in metabolism and homeostasis. New reviews at intervals are therefore clearly warranted. The pathways of complement activation, the function of the complement system, and the interaction between complement and coagulation, inflammation, and the adaptive immune system in relation to xenotransplantation are reviewed. Through several different mechanisms, complement activation is a major factor in contributing to xenograft failure. In the organ\u2010source pig, the detrimental influence of the complement system is seen during organ harvest and preservation, for example, in ischemia\u2010reperfusion injury. In the recipient, the effect of complement can be seen through its interaction with the immune, coagulation, and inflammatory responses. Genetic\u2010engineering and other therapeutic methods by which the xenograft can be protected from the effects of complement activation are discussed. The review provides an updated source of reference to this increasingly complex subject.<\/jats:p>","DOI":"10.1111\/xen.12517","type":"journal-article","created":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T11:29:28Z","timestamp":1556537368000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["The complex functioning of the complement system in xenotransplantation"],"prefix":"10.1111","volume":"26","author":[{"given":"Hongmin","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery, Tongji Hospital Tongji Medical College, Huazhong University of Science and Technology Wuhan China"},{"name":"Xenotransplantation Program, Department of Surgery University of Alabama at Birmingham Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetaka","family":"Hara","sequence":"additional","affiliation":[{"name":"Xenotransplantation Program, Department of Surgery University of Alabama at Birmingham Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8899-9431","authenticated-orcid":false,"given":"David K. 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