Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States.
Department of Biomedical Sciences, University of Oakland University School of Medicine, Rochester, MI, United States.
Mol Immunol. 2018 Oct;102:58-72. doi: 10.1016/j.molimm.2018.05.018. Epub 2018 Jun 27.
Properdin, the widely known positive regulator of the alternative pathway (AP), has undergone significant investigation over the last decade to define its function in inflammation and disease, including its role in arthritis, asthma, and kidney and cardiovascular diseases. Properdin is a glycoprotein found in plasma that is mainly produced by leukocytes and can positively regulate AP activity by stabilizing C3 and C5 convertases and initiating the AP. Promotion of complement activity by properdin results in changes in the cellular microenvironment that contribute to innate and adaptive immune responses, including pro-inflammatory cytokine production, immune cell infiltration, antigen presenting cell maturation, and tissue damage. The use of properdin-deficient mouse models and neutralizing antibodies has contributed to the understanding of the mechanisms by which properdin contributes to promoting or preventing disease pathology. This review mainly focusses on the multifaceted roles of properdin in inflammation and diseases, and how understanding these roles is contributing to the development of new disease therapies.
备解素,即众所周知的补体旁路途径(AP)的正向调节剂,在过去十年中经历了大量的研究,以明确其在炎症和疾病中的功能,包括其在关节炎、哮喘以及肾脏和心血管疾病中的作用。备解素是一种在血浆中发现的糖蛋白,主要由白细胞产生,可以通过稳定 C3 和 C5 转化酶和启动 AP 来正向调节 AP 活性。备解素促进补体活性会导致细胞微环境发生变化,从而促进先天和适应性免疫反应,包括促炎细胞因子的产生、免疫细胞浸润、抗原呈递细胞成熟和组织损伤。使用备解素缺陷型小鼠模型和中和抗体有助于理解备解素促进或预防疾病病理的机制。这篇综述主要关注备解素在炎症和疾病中的多方面作用,以及了解这些作用如何有助于开发新的疾病治疗方法。