CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, Coimbra, Portugal.
PLoS One. 2012;7(10):e48391. doi: 10.1371/journal.pone.0048391. Epub 2012 Oct 31.
Defective clearance of apoptotic cells has emerged as an important contributing factor to the pathogenesis of many diseases. Although many efforts have been made to understand the machinery involved in the recognition between phagocytes and potential targets, little is known about the intracellular transport of phagosomes containing apoptotic cells within mammalian cells. We have, therefore, performed a detailed study on the maturation of phagosomes containing apoptotic cells in a non-professional phagocytic cell line. This process was compared with the maturation of IgG-opsonized particles, which are internalized via the Fcγ-receptor (Fcγ-R), one of the best characterized phagocytic receptor, in the same cell line stably expressing the Fcγ-RIIA. By comparing markers from different stages of phagosome maturation, we have found that phagosomes carrying apoptotic particles reach the lysosomes with a delay compared to those containing IgG-opsonized particles. Enrichment of the apoptotic particles in phosphatidylserine (PS) neither changed the kinetics of their engulfment nor the maturation process of the phagosome.
凋亡细胞的清除功能缺陷已成为许多疾病发病机制的一个重要因素。尽管人们已经做出许多努力来了解吞噬细胞与潜在靶细胞之间相互识别的机制,但对于在哺乳动物细胞内包含凋亡细胞的吞噬体的细胞内运输过程却知之甚少。因此,我们在一个非专业吞噬细胞系中对包含凋亡细胞的吞噬体的成熟过程进行了详细的研究。该过程与 IgG 包被颗粒的成熟过程进行了比较,这些颗粒通过 Fcγ 受体(Fcγ-R)内化,Fcγ-R 是在稳定表达 Fcγ-RIIA 的同一细胞系中被充分鉴定的吞噬受体之一。通过比较不同阶段的吞噬体成熟标志物,我们发现与含有 IgG 包被颗粒的吞噬体相比,携带凋亡颗粒的吞噬体到达溶酶体的时间延迟。凋亡颗粒中富含磷脂酰丝氨酸(PS)既不会改变它们的吞噬动力学,也不会改变吞噬体的成熟过程。