Brain pericytes increase the lipopolysaccharide-enhanced transcytosis of HIV-1 free virus across the in vitro blood–brain barrier: evidence for cytokine-mediated pericyte-endothelial cell crosstalk

Fluids and Barriers of the CNS

William A Banks²  Shinya Dohgu¹ 

[1] Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan;Geriatrics Research Education and Clinical Center, Puget Sound Health Care System, Seattle WA and Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Bldg 1/Rm 810A, VAPSHCS, 1660 S. Columbian Way, Seattle, WA 98108, USA

关键词: Lipopolysaccharide;    Neuroimmune;    Neuroinflammation;    AIDS;    BMEC;    Cytokines;    Brain endothelial cells;    Pericytes;    HIV-1;    Blood–brain barrier;   

Others  :  806559
DOI  :  10.1186/2045-8118-10-23

 received in 2012-11-16, accepted in 2013-06-23,  发布年份 2013

【 摘 要 】

Background

Human immunodeficiency virus-1 (HIV-1) enters the brain by crossing the blood–brain barrier (BBB) as both free virus and within infected immune cells. Previous work showed that activation of the innate immune system with lipopolysaccharide (LPS) enhances free virus transport both in vivo and across monolayer monocultures of brain microvascular endothelial cells (BMECs) in vitro.

Methods

Here, we used monocultures and co-cultures of brain pericytes and brain endothelial cells to examine the crosstalk between these cell types in mediating the LPS-enhanced permeation of radioactively-labeled HIV-1 (I-HIV) across BMEC monolayers.

Results

We found that brain pericytes when co-cultured with BMEC monolayers magnified the LPS-enhanced transport of I-HIV without altering transendothelial electrical resistance, indicating that pericytes affected the transcytotic component of HIV-1 permeation. As LPS crosses the BBB poorly if at all, and since pericytes are on the abluminal side of the BBB, we postulated that luminal LPS acts indirectly on pericytes through abluminal secretions from BMECs. Consistent with this, we found that the pattern of secretion of cytokines by pericytes directly exposed to LPS was different than when the pericytes were exposed to the abluminal fluid from LPS-treated BMEC monolayers.

Conclusion

These results are evidence for a cellular crosstalk in which LPS acts at the luminal surface of the brain endothelial cell, inducing abluminal secretions that stimulate pericytes to release substances that enhance the permeability of the BMEC monolayer to HIV.

【 授权许可】

   
2013 Dohgu and Banks; licensee BioMed Central Ltd.

【 图 表 】

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