Bucki Robert, Levental Ilya, Kulakowska Alina, Janmey Paul A
University of Pennsylvania, Institute for Medicine and Engineering, Vagelos Research Laboratories, Philadelphia, PA 19104, USA.
Curr Protein Pept Sci. 2008 Dec;9(6):541-51. doi: 10.2174/138920308786733912.
Gelsolin is a highly conserved, multifunctional actin-binding protein initially described in the cytosol of macrophages and subsequently identified in many vertebrate cells. A unique property of gelsolin is that in addition to its widely recognized function as a cytoplasmic regulator of actin organization, the same gene expresses a splice variant coding for a distinct isoform, plasma gelsolin, which is secreted into extracellular fluids. The secreted form of gelsolin has been implicated in a number of processes such as the extracellular actin scavenging system and the presentation of lysophosphatidic acid and other inflammatory mediators to their receptors, in addition to its function as a substrate for extracellular matrix-modulating enzymes. Consistent with these proposed functions, blood gelsolin levels decrease markedly in a variety of clinical conditions such as acute respiratory distress syndrome, sepsis, major trauma, prolonged hyperoxia, malaria, and liver injury. This correlation between blood gelsolin levels and critical clinical conditions suggests the potential utility of gelsolin as a prognostic marker as well as the possibility for therapeutic replenishment of gelsolin to alleviate the injurious cascades in these settings. This review summarizes current data supporting a role of plasma gelsolin in extracellular fluids and the potential for its use as a diagnostic marker or therapeutic treatment in several medical conditions.
凝溶胶蛋白是一种高度保守的多功能肌动蛋白结合蛋白，最初在巨噬细胞的细胞质中被描述，随后在许多脊椎动物细胞中被鉴定出来。凝溶胶蛋白的一个独特特性是，除了其作为肌动蛋白组织的细胞质调节剂这一广为人知的功能外，同一基因还表达一种剪接变体，编码一种不同的异构体——血浆凝溶胶蛋白，它被分泌到细胞外液中。除了作为细胞外基质调节酶的底物这一功能外，凝溶胶蛋白的分泌形式还参与了许多过程，如细胞外肌动蛋白清除系统以及溶血磷脂酸和其他炎症介质向其受体的呈递。与这些提出的功能一致，在多种临床状况下，如急性呼吸窘迫综合征、败血症、重大创伤、长期高氧、疟疾和肝损伤，血液中凝溶胶蛋白水平会显著降低。血液凝溶胶蛋白水平与危急临床状况之间的这种相关性表明，凝溶胶蛋白作为一种预后标志物具有潜在用途，同时也存在通过补充凝溶胶蛋白来减轻这些情况下损伤级联反应的治疗可能性。这篇综述总结了当前支持血浆凝溶胶蛋白在细胞外液中作用的数据，以及其在几种医学状况下作为诊断标志物或治疗手段的潜在用途。
