Group V Secretory Phospholipase A2 Reveals Its Role in House Dust Mite-Induced Allergic Pulmonary Inflammation by Regulation of Dendritic Cell Function
Group V Secretory Phospholipase A2 Reveals Its Role in House Dust Mite-Induced Allergic Pulmonary Inflammation by Regulation of Dendritic Cell Function
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DOI：
10.4049/jimmunol.1001384
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发表时间：
2010-10-01
影响因子：
4.4
通讯作者：
Balestrieri, Barbara
中科院分区：
文献类型：
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作者：
Giannattasio, Giorgio;Fujioka, Daisuke;Balestrieri, Barbara
我们先前已经表明，V组分泌型磷脂酶A（2）（sPLA（2））调节酵母聚糖和白色念珠菌的吞噬作用的机制，这取决于吞噬体与巨噬细胞中晚期内体的融合。在这项研究中，我们报告了第V组sPLA（2）（Pla 2g 5）-null小鼠暴露于屋尘螨粉尘螨提取物中，与野生型（WT）小鼠相比，肺部炎症和杯状细胞化生明显减少。Pla 2g 5基因敲除小鼠对D. farinae与WT小鼠比较。Pla 2g 5-null骨髓来源的树突状细胞（BMDCs）被D. farinae的细胞内处理过敏原的延迟和过敏原依赖性成熟受损，这一模式由D.淀粉激发的小鼠。转移到D。Pla 2g 5基因敲除的BMDCs比D.在WT小鼠中，用负载有淀粉的WT BMDC诱导肺部炎症和Th 2极化。然而，Pla 2g 5-null受体与WT或Pla 2g 5-null D一起转移。淀粉负载的BMDCs表现出显著降低的局部炎症反应。尽管WT BMDC的转移仍然在局部淋巴结中诱导了完整的Th 2细胞因子反应，但在farinae中。因此，V组sPLA（2）在APC中的表达调节DC的Ag加工和成熟，并有助于肺部炎症和针对D.花粉此外，另一种待鉴定的驻留细胞类型对于肺部炎症的发展是必不可少的，可能是其中V组sPLA（2）被D上调的细胞。farinae，其功能也受V组sPLA的调节（2）。免疫学杂志，2010，185：4430-4438。
We have previously shown that group V secretory phospholipase A(2) (sPLA(2)) regulates phagocytosis of zymosan and Candida albicans by a mechanism that depends on fusion of phagosomes with late endosomes in macrophages. In this study, we report that group V sPLA(2) (Pla2g5)-null mice exposed to an extract of house dust mite Dermatophagoides farinae had markedly reduced pulmonary inflammation and goblet cell metaplasia compared with wild-type (WT) mice. Pla2g5-null mice had also impaired Th2-type adaptive immune responses to D. farinae compared with WT mice. Pla2g5-null bone marrow-derived dendritic cells (BMDCs) activated by D. farinae had delayed intracellular processing of allergen and impaired allergen-dependent maturation, a pattern recapitulated by the native lung DCs of D. farinae-challenged mice. Adoptively transferred D. farinae-loaded Pla2g5-null BMDCs were less able than D. farinae-loaded WT BMDCs to induce pulmonary inflammation and Th2 polarization in WT mice. However, Pla2g5-null recipients transferred with WT or Pla2g5-null D. farinae-loaded BMDCs exhibited significantly reduced local inflammatory responses to D. farinae, even though the transfer of WT BMDCs still induced an intact Th2 cytokine response in regional lymph nodes. Thus, the expression of group V sPLA(2) in APCs regulates Ag processing and maturation of DCs and contributes to pulmonary inflammation and immune response against D. farinae. Furthermore, an additional yet to be identified resident cell type is essential for the development of pulmonary inflammation, likely a cell in which group V sPLA(2) is upregulated by D. farinae, and whose function is also regulated by group V sPLA(2). The Journal of Immunology, 2010, 185: 4430-4438.