West M A, Antoniou A N, Prescott A R, Azuma T, Kwiatkowski D J, Watts C
Department of Biochemistry, University of Dundee, Dundee, GB.
Eur J Immunol. 1999 Nov;29(11):3450-5. doi: 10.1002/(SICI)1521-4141(199911)29:11<3450::AID-IMMU3450>3.0.CO;2-A.
Previous studies have shown that mice lacking the actin-severing and capping protein gelsolin have defects in leukocyte and platelet function. Moreover, dermal fibroblasts from gelsolin knockout (Gsn(-)) mice showed substantially reduced motility, membrane ruffling and pinocytosis. We have generated dendritic cells (DC) from spleens of Gsn(-) mice to investigate the importance of gelsolin in antigen endocytosis and processing. We show here that Gsn(-) DC produce apparently normal membrane ruffles which can resolve to form large macropinosomes. Moreover, presentation of exogenous antigens on both MHC class II and class I molecules was equivalent in Gsn(-) and wild-type DC. Thus the major rearrangements of the actin cytoskeleton needed for DC antigen uptake and presentation can proceed in the absence of a major actin filament regulatory protein.
先前的研究表明,缺乏肌动蛋白切断和封端蛋白凝溶胶蛋白的小鼠在白细胞和血小板功能方面存在缺陷。此外,来自凝溶胶蛋白基因敲除(Gsn(-))小鼠的真皮成纤维细胞表现出明显降低的运动性、膜褶皱和胞饮作用。我们从Gsn(-)小鼠的脾脏中生成了树突状细胞(DC),以研究凝溶胶蛋白在抗原内吞作用和加工过程中的重要性。我们在此表明,Gsn(-) DC产生的膜褶皱明显正常,这些膜褶皱可以分解形成大型巨胞饮体。此外,在MHC II类和I类分子上呈递外源性抗原在Gsn(-) DC和野生型DC中是相同的。因此,在没有主要肌动蛋白丝调节蛋白的情况下,DC抗原摄取和呈递所需的肌动蛋白细胞骨架的主要重排仍可进行。