Santoni A, Gismondi A, Morrone S, Procopio A, Modesti A, Scarpa S, D'Orazi G, Piccoli M, Frati L
Department of Experimental Medicine, University of L'Aquila, Rome, Italy.
J Immunol. 1989 Oct 1;143(7):2415-21.
The ability of NK cells to synthesize and secrete fibronectin (FN), an extracellular matrix glycoprotein which plays a key role in many biologic processes including cellular adhesion, morphology, cytoskeletal organization, cell migration, and invasiveness, was studied. By using affinity-purified polyclonal antibodies directed against human cellular or plasma FN, the presence of FN was evidentiated on Percoll-purified rat large granular lymphocyte or on a large granular lymphocyte tumor cell line (CRC) by flow cytometry and immunoelectron microscopy. Its expression increased after NK cell activation by poly I:C administration. Biochemical analysis by immunoprecipitation and SDS-PAGE indicated that FN was associated to cell surface and secreted in the supernatant in a molecular form similar to that of FN from L929 fibroblasts. In an attempt to understand the role of FN in the NK cell function, we found that an antibody against human plasma FN and its F(ab')2 fragment inhibited NK cytotoxicity against YAC-1 target at the effector cell level. Inhibition occurred at the postbinding level, because F(ab')2 anti-FN inhibited induction of phosphatidylinositol hydrolysis by YAC-1 target cells, whereas binding to target cells was not affected. The possible role of FN in the NK cytotoxic function is suggested.
研究了自然杀伤（NK）细胞合成和分泌纤连蛋白（FN）的能力，纤连蛋白是一种细胞外基质糖蛋白，在包括细胞黏附、形态、细胞骨架组织、细胞迁移和侵袭性在内的许多生物学过程中起关键作用。通过使用针对人细胞或血浆FN的亲和纯化多克隆抗体，通过流式细胞术和免疫电子显微镜在Percoll纯化的大鼠大颗粒淋巴细胞或大颗粒淋巴细胞肿瘤细胞系（CRC）上证实了FN的存在。通过给予聚肌苷酸:聚胞苷酸（poly I:C）激活NK细胞后，其表达增加。通过免疫沉淀和十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）进行的生化分析表明，FN与细胞表面相关，并以与L929成纤维细胞的FN相似的分子形式分泌到上清液中。为了试图了解FN在NK细胞功能中的作用，我们发现针对人血浆FN的抗体及其F(ab')2片段在效应细胞水平抑制NK细胞对YAC-1靶细胞的细胞毒性。抑制发生在结合后水平，因为F(ab')2抗FN抑制YAC-1靶细胞诱导的磷脂酰肌醇水解，而与靶细胞的结合不受影响。提示了FN在NK细胞毒性功能中的可能作用。
