Centre for Vascular Research, University of New South Wales, Sydney, Australia.
Traffic. 2011 Dec;12(12):1730-43. doi: 10.1111/j.1600-0854.2011.01272.x. Epub 2011 Sep 21.
The biochemical composition and biophysical properties of cell membranes are hypothesized to affect cellular processes such as phagocytosis. Here, we examined the plasma membranes of murine macrophage cell lines during the early stages of uptake of immunoglobulin G (IgG)-coated polystyrene particles. We found that the plasma membrane undergoes rapid actin-independent condensation to form highly ordered phagosomal membranes, the biophysical hallmark of lipid rafts. Surprisingly, these membranes are depleted of cholesterol and enriched in sphingomyelin and ceramide. Inhibition of sphingomyelinase activity impairs membrane condensation, F-actin accumulation at phagocytic cups and particle uptake. Switching phagosomal membranes to a cholesterol-rich environment had no effect on membrane condensation and the rate of phagocytosis. In contrast, preventing membrane condensation with the oxysterol 7-ketocholesterol, even in the presence of ceramide, blocked F-actin dissociation from nascent phagosomes and particle uptake. In conclusion, our results suggest that ordered membranes function to co-ordinate F-actin remodelling and that the biophysical properties of phagosomal membranes are essential for phagocytosis.
细胞膜的生化组成和生物物理特性被假设会影响细胞过程，如吞噬作用。在这里，我们研究了在摄取 IgG 包裹的聚苯乙烯颗粒的早期阶段，鼠巨噬细胞系的质膜。我们发现质膜迅速进行肌动蛋白非依赖性凝聚，形成高度有序的吞噬小体膜，这是脂筏的生物物理特征。令人惊讶的是，这些膜中胆固醇含量减少，鞘磷脂和神经酰胺含量增加。抑制鞘磷脂酶活性会损害膜凝聚、吞噬杯处 F-肌动蛋白的积累和颗粒摄取。将吞噬小体膜转换为富含胆固醇的环境对膜凝聚和吞噬作用的速率没有影响。相比之下，即使存在神经酰胺，用氧化固醇 7-酮胆固醇阻止膜凝聚也会阻止新生吞噬小体中 F-肌动蛋白的解离和颗粒摄取。总之，我们的结果表明，有序的膜有助于协调 F-肌动蛋白重塑，并且吞噬小体膜的生物物理特性对于吞噬作用是必不可少的。
