Rovere P, Peri G, Fazzini F, Bottazzi B, Doni A, Bondanza A, Zimmermann V S, Garlanda C, Fascio U, Sabbadini M G, Rugarli C, Mantovani A, Manfredi A A
Tumor Immunology Laboratory, Istituto Scientifico H S. Raffaele, Milano, Italy.
Blood. 2000 Dec 15;96(13):4300-6.
Pentraxins are acute-phase proteins produced in vivo during inflammatory reactions. Classical short pentraxins, C-reactive protein, and serum amyloid P component are generated in the liver in response to interleukin (IL)-6. The long pentraxin PTX3 is produced in tissues under the control of primary proinflammatory signals, such as lipopolysaccharide, IL-1 beta, and tumor necrosis factor-alpha, which also promote maturation of dendritic cells (DCs). Cell death commonly occurs during inflammatory reactions. In this study, it is shown that PTX3 specifically binds to dying cells. The binding was dose dependent and saturable. Recognition was restricted to extranuclear membrane domains and to a chronological window after UV irradiation or after CD95 cross-linking-induced or spontaneous cell death in vitro. PTX3 bound to necrotic cells to a lesser extent. Human DCs failed to internalize dying cells in the presence of PTX3, while they took up normally soluble or inert particulate substrates. These results suggest that PTX3 sequesters cell remnants from antigen-presenting cells, possibly contributing to preventing the onset of autoimmune reactions in inflamed tissues. (Blood. 2000;96:4300-4306)
五聚素是炎症反应期间在体内产生的急性期蛋白。经典的短五聚素、C反应蛋白和血清淀粉样蛋白P成分是肝脏在白细胞介素（IL）-6的作用下生成的。长五聚素PTX3是在诸如脂多糖、IL-1β和肿瘤坏死因子-α等主要促炎信号的控制下在组织中产生的，这些信号也促进树突状细胞（DC）的成熟。细胞死亡在炎症反应中通常会发生。在本研究中，结果表明PTX3特异性结合死亡细胞。这种结合是剂量依赖性的且具有饱和性。识别仅限于核外膜结构域以及紫外线照射后或体外CD95交联诱导的或自发性细胞死亡后的一个时间窗。PTX3与坏死细胞的结合程度较低。在有PTX3存在的情况下，人DC不能内化死亡细胞，而它们能正常摄取可溶性或惰性颗粒底物。这些结果提示PTX3从抗原呈递细胞中隔离细胞残骸，可能有助于防止炎症组织中自身免疫反应的发生。（《血液》。2000年；96：4300 - 4306）
