Group V Secretory Phospholipase A2 Modulates Phagosome Maturation and Regulates the Innate Immune Response against Candida albicans
Group V Secretory Phospholipase A2 Modulates Phagosome Maturation and Regulates the Innate Immune Response against Candida albicans
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DOI：
10.4049/jimmunol.0803776
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发表时间：
2009-04-15
影响因子：
4.4
通讯作者：
Arm, Jonathan P.
中科院分区：
文献类型：
--
作者：
Balestrieri, Barbara;Maekawa, Akiko;Arm, Jonathan P.
磷脂酶A（2）（PLA（2））水解细胞膜磷脂的sn-2位置以释放脂肪酸和溶血磷脂。我们以前曾报道，V组分泌型PLA（2）（sPLA（2））从小鼠腹腔巨噬细胞的高尔基体和再循环内体移位到新形成的吞噬体，并调节酵母聚糖的吞噬作用，表明在先天免疫中的作用。在这里，我们报道了在缺乏V组sPLA的巨噬细胞中，吞噬体成熟在早期时间点减少50-60%，而酵母聚糖的结合未受损。V组sPLA（2）调节吞噬作用的能力扩展到IgG和补体调理的绵羊RBC的吞噬作用。此外，缺乏V组sPLA的巨噬细胞在吞噬作用、吞噬体成熟和杀死白色念珠菌方面具有延迟。细胞因子的产生和类花生酸的产生并不因缺乏V组sPLA而受损（2）。此外，在系统性念珠菌病模型中，缺乏V组sPLA（2）的小鼠在感染后第7天肾脏、肝脏和脾脏中的真菌负荷增加，死亡率增加。因此，V组sPLA通过主要的吞噬受体调节吞噬作用，并通过调节吞噬作用和通过可能依赖于吞噬溶酶体融合的机制杀死来促进针对白色念珠菌的先天性免疫应答。免疫学杂志，2009，182：4891-4898.
Phospholipase A(2) (PLA(2)) hydrolyzes the sn-2 position of cell membrane phospholipids to release fatty acids and lysophospholipids. We have previously reported that group V secretory PLA(2) (sPLA(2)) translocates from the Golgi and recycling endosomes of mouse peritoneal macrophages to newly formed phagosomes and regulates the phagocytosis of zymosan, suggesting a role in innate immunity. Here we report that in macrophages lacking group V sPLA(2), phagosome maturation was reduced 50-60% at early time points while the binding of zymosan was unimpaired. The ability of group V sPLA(2) to regulate phagocytosis extended to phagocytosis of IgG- and complement-opsonized sheep RBC. Moreover, macrophages lacking group V sPLA, had delays in phagocytosis, phagosome maturation, and killing of Candida albicans. Cytokine production and eicosanoid generation were not impaired by the lack of group V sPLA(2). Furthermore, in a model of systemic candidiasis, mice lacking group V sPLA(2) had an increased fungal burden in the kidney, liver, and spleen at day 7 postinfection and increased mortality. Thus, group V sPLA, regulates phagocytosis through major phagocytic receptors and contributes to the innate immune response against C albicans by regulating phagocytosis and killing through a mechanism that is likely dependent on phagolysosome fusion. The Journal of Immunology, 2009, 182: 4891-4898.