Hart Melanie L, Walsh Mary C, Stahl Gregory L
Department of Anesthesiology, Perioperative & Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Thorn 705, 75 Francis Street, Boston, MA 02115, USA.
Mol Immunol. 2004 Jun;41(2-3):165-71. doi: 10.1016/j.molimm.2004.03.013.
Ischemia and reperfusion of organs/tissues induce a state of inflammation that can lead to tissue injury. Focus on development of effective therapeutics based on sound pre-clinical work and the role of leukocytes in models of human disease has not lead to a successful clinical trial for anti-leukocyte technologies. For the past >30 years, it has been known that complement activation plays a role in the inflammation and tissue injury associated with ischemia/reperfusion (I/R) injury. In the last 10 years, several complement inhibitors have made their way from the bench to bedside. Will a complement inhibitor eventually be approved for clinical treatment of I/R type diseases? What pathway(s) are involved in I/R injury, and what role do they play? What specific complement components are needed for resolution of inflammation and what components need to be inhibited to decrease tissue injury? This short review will focus on the current state of the art knowledge about complement, complement pathways, complement components and several promising clinical biologics that inhibit complement activation. This review is not a complete review of complement in ischemia/reperfusion injury, but it raises important questions about the role of complement, its pathways and the current knowledge in the area of ischemia/reperfusion injury.
器官/组织的缺血再灌注会引发炎症状态，进而导致组织损伤。基于扎实的临床前研究致力于开发有效疗法，且关注白细胞在人类疾病模型中的作用，但尚未促成抗白细胞技术的成功临床试验。在过去30多年里，人们已经知道补体激活在与缺血/再灌注（I/R）损伤相关的炎症和组织损伤中起作用。在过去10年里，几种补体抑制剂已从实验室走向临床。补体抑制剂最终会被批准用于I/R型疾病的临床治疗吗？I/R损伤涉及哪些途径，它们发挥着什么作用？炎症消退需要哪些特定的补体成分，需要抑制哪些成分以减少组织损伤？这篇简短的综述将聚焦于关于补体、补体途径、补体成分以及几种有前景的抑制补体激活的临床生物制剂的当前最新知识。本综述并非对缺血/再灌注损伤中补体的全面综述，但它提出了关于补体的作用、其途径以及缺血/再灌注损伤领域当前知识的重要问题。
