基础免疫学基础免疫学1rom defense of the single cell to guardian of the intravascular space.pdf

HHS Public Access Author manuscript A Immunol Rev. Author manuscript; available in PMC 2017 November 01. u t h Published in final edited form as: o r Immunol Rev. 2016 November ; 274(1): 9–15. doi:10.1111/imr.12474. M a n u s c Evolution of the complement system: from defense of the single r i p t cell to guardian of the intravascular space Michelle Elvington, M. Kathryn Liszewski, and John P. Atkinson Department of Internal Medicine, Division of Rheumatology, Washington University School of Medicine, Saint Louis, MO 63110, USA A u Abstract t h o The complement system is an evolutionarily ancient component of immunity that revolves around r M the central component C3. With the recent description of intracellular C3 stores in many types of a human cells, our view of the complement system has expanded. In this article, we hypothesize that n u s a primitive version of C3 comprised the first element of the original complement system and c r initially functioned intracellularly and on the membrane of single-cell organisms. With increasing i p t specialization and multicellularity, C3 evolved a secretory capacity that allowed it to play a protective role in the interstitial space. Upon development of a pumped circulatory system, C3 was synthesized in large amounts and secreted by the liver to protect the intravascular space. Recent discoveries of intracellular C3 activation, a C3-based recycling pathway and C3 being a driver and programmer of cell metabolism suggest that the complement system utilizes C3 to guard not only extracellular but als