ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48.
ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48.
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DOI：
10.1038/ncomms3479
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发表时间：
2013
影响因子：
16.6
通讯作者：
Sriramarao, P.
中科院分区：
文献类型：
--
作者：
Ha, Sung Gil;Ge, Xiao Na;Bahaie, Nooshin S.;Kang, Bit Na;Rao, Amrita;Rao, Savita P.;Sriramarao, P.
ORM（酵母）样蛋白异构体3（ORMDL 3）最近被确定为哮喘易感性的候选基因，但其导致哮喘发病的机制尚不清楚。在这里，我们证明了ORMDL 3在过敏性炎症背景下嗜酸性粒细胞中的功能作用。招募到过敏原激发小鼠气道的嗜酸性粒细胞表达ORMDL 3。骨髓嗜酸性粒细胞中的ORMDL 3表达定位于内质网中，并由IL-3和eotaxin-1诱导。ORMDL 3在嗜酸性粒细胞中的过表达导致滚动增加、明显的细胞骨架重排、ERK（1/2）磷酸化和NF-κB核转位。ORMDL 3的敲低显著抑制体内活化诱导的细胞形状变化、粘附和募集至炎症部位，并降低CD 49 d和CD 18的表达。此外，ORMDL 3调节IL-3诱导的CD 48表达和CD 48介导的嗜酸性粒细胞脱粒。这些研究表明，ORMDL 3调节嗜酸性粒细胞的运输，募集和脱粒，进一步阐明了这种分子在过敏性哮喘和其他可能的嗜酸性粒细胞疾病中的作用。
ORM (yeast)-Like protein isoform 3 (ORMDL3) has recently been identified as a candidate gene for susceptibility to asthma; however the mechanisms by which it contributes to asthma pathogenesis are not well understood. Here we demonstrate a functional role for ORMDL3 in eosinophils in the context of allergic inflammation. Eosinophils recruited to the airways of allergen-challenged mice express ORMDL3. ORMDL3 expression in bone marrow eosinophils is localized in the endoplasmic reticulum and is induced by IL-3 and eotaxin-1. Over-expression of ORMDL3 in eosinophils causes increased rolling, distinct cytoskeletal rearrangement, ERK (1/2) phosphorylation and nuclear translocation of NF-κB. Knock-down of ORMDL3 significantly inhibits activation-induced cell shape changes, adhesion and recruitment to sites of inflammation in vivo, combined with reduced expression of CD49d and CD18. Additionally, ORMDL3 regulates IL-3-induced expression of CD48 and CD48-mediated eosinophil degranulation. These studies show that ORMDL3 regulates eosinophil trafficking, recruitment and degranulation, further elucidating a role for this molecule in allergic asthma and potentially other eosinophilic disorders.
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DOI：
10.4049/jimmunol.1102253
发表时间：
2012-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bahaie NS;Hosseinkhani MR;Ge XN;Kang BN;Ha SG;Blumenthal MS;Jessberger R;Rao SP;Sriramarao P
通讯作者：
Sriramarao P
影响因子：
6.1
作者：
Coward, WR;Sagara, H;Church, MK
通讯作者：
Church, MK
影响因子：
4.8
作者：
Bahaie, Nooshin S.;Kang, Bit Na;Sriramarao, P.
通讯作者：
Sriramarao, P.
DOI：
10.1152/ajplung.00005.2012
发表时间：
2012-06-01
影响因子：
4.9
作者：
Kang, Bit Na;Ha, Sung Gil;Sriramarao, P.
通讯作者：
Sriramarao, P.
影响因子：
2.7
作者：
Hrdlickova, Barbara;Holla, Lydie Izakovicova
通讯作者：
Holla, Lydie Izakovicova