IL-4 increases CD21-dependent infection of pulmonary alveolar epithelial type II cells by EBV

被引:7
作者
Malizia, Andrea P. [1 ,2 ]
Egan, Jim J. [2 ]
Doran, Peter P. [1 ]
机构
[1] Univ Coll Dublin, Sch Med & Med Sci, Clin Res Ctr, Dublin 7, Ireland
[2] Mater Misericordiae Univ Hosp, Adv Lung Dis & Lung Transplant Program, Dublin 7, Ireland
关键词
Idiopathic pulmonary fibrosis; Alveolar epithelial cells; EBV; CD21; IL-4; EPSTEIN-BARR-VIRUS; REPLICATION; RECEPTOR; ROLES; DNA;
D O I
10.1016/j.molimm.2009.01.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
EBV infection has been implicated in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). Viral infection may occur from the early or late stage in IPF development. Whether alveolar epithelial cells, AECs, normally express EBV main receptor, CD21, remains uncertain. Such situations prompted us to exploit an efficient direct infection system to investigate EBV receptor repertoire in primary human AECs. Using human primary type 2 AECs, which have been grown in basal medium supplemented with 10 ng/ml Keratinocyte Growth Factor, and type 1 AECs, supplemented with Epithelial Growth Factor, both AEC lines express CD21 mRNA and protein with a significant increase in type 2 cells. Type 2 AECs have been exposed to TGF beta 1 and IL-4, whose expression is associated with IPF development. CD21 is highly expressed in type 2 AECs following IL-4 exposure. EBV bound to type 2 AECs membrane increases significantly following pre-treatment with IL-4 (p < 0.001) and decreasing antagonizing CD21 receptor (p < 0.01). 200 mu g/ml G418-mediated selection of EBV-Neomycin resistant infected cells selected IL-4 pre-exposed type 2 AECs. Our study of a viral cell line model provides evidence to suggest that CD21-dependent viral entry plays a crucial role in type 2 AECs, indicative of an IL-4 response EBV infection in IPF (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1905 / 1910
页数:6
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