Properdin and factor h: opposing players on the alternative complement pathway "see-saw".
Properdin and factor h: opposing players on the alternative complement pathway "see-saw".
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DOI：
10.3389/fimmu.2013.00093
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发表时间：
2013
影响因子：
7.3
通讯作者：
Kishore U
中科院分区：
文献类型：
--
作者：
Kouser L;Abdul-Aziz M;Nayak A;Stover CM;Sim RB;Kishore U
Properdin和因子H是在补体途径中具有相反功能的两个关键调控蛋白。Properdin通过稳定C3bBb复合物而上调替代途径，而因子H通过促进C3b的蛋白水解降解而下调替代途径。虽然H因子主要在肝脏中产生，但也有一些肝外来源。除肝脏外，H因子也在胎儿小管、角化细胞、皮肤成纤维细胞、眼组织、脂肪组织、脑、肺、心脏、脾脏、胰腺、肾脏、肌肉和胎盘中合成。中性粒细胞是properdin的主要来源，它也由单核细胞、T细胞和骨髓祖细胞系产生。在n -甲酰基蛋氨酸-亮氨酸-苯丙氨酸（fMLP）和肿瘤坏死因子α (TNF-α)的刺激下，中性粒细胞从细胞内储存中释放Properdin。来源于人肝脏的HEP G2细胞已被发现能产生功能性的properdin。内皮细胞在受剪切应力诱导时也产生适当素，因此是血浆适当素的生理来源。合成这两种补体调节因子的肝外位点的多样性表明了蛋白质局部可用性的重要性和必要性。在这里，我们讨论了properdin和因子H的局部合成的重要性。鉴于最近发现的properdin和因子H的意想不到的和新的作用，这就具有更大的重要性，这些作用可能独立于它们在补体调节中的参与。
Properdin and factor H are two key regulatory proteins having opposite functions in the alternative complement pathway. Properdin up-regulates the alternative pathway by stabilizing the C3bBb complex, whereas factor H downregulates the pathway by promoting proteolytic degradation of C3b. While factor H is mainly produced in the liver, there are several extrahepatic sources. In addition to the liver, factor H is also synthesized in fetal tubuli, keratinocytes, skin fibroblasts, ocular tissue, adipose tissue, brain, lungs, heart, spleen, pancreas, kidney, muscle, and placenta. Neutrophils are the major source of properdin, and it is also produced by monocytes, T cells and bone marrow progenitor cell line. Properdin is released by neutrophils from intracellular stores following stimulation by N-formyl-methionine-leucine-phenylalanine (fMLP) and tumor necrosis factor alpha (TNF-α). The HEP G2 cells derived from human liver has been found to produce functional properdin. Endothelial cells also produce properdin when induced by shear stress, thus is a physiological source for plasma properdin. The diverse range of extrahepatic sites for synthesis of these two complement regulators suggests the importance and need for local availability of the proteins. Here, we discuss the significance of the local synthesis of properdin and factor H. This assumes greater importance in view of recently identified unexpected and novel roles of properdin and factor H that are potentially independent of their involvement in complement regulation.
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