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Clin Immunol. 2014 May-Jun;152(1-2):90-100. doi: 10.1016/j.clim.2014.03.004. Epub 2014 Mar 18.

t-PA acts as a cytokine to regulate lymphocyte-endothelium adhesion in experimental autoimmune encephalomyelitis.

Author information

1
Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
2
Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
3
Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China. Electronic address: sunbo720@yahoo.com.cn.
4
Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China; Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin, Heilongjiang 150086, China. Electronic address: lihulun@yahoo.com.cn.

Abstract

In this study, the capacity for t-PA to affect T cell-brain microvascular endothelial cell adhesion by acting as a cytokine was investigated. Following the treatment of a brain-derived endothelial cell line, bEnd.3, with various concentrations of t-PA, adhesion and transwell migration assays were performed. In the presence of t-PA, enhanced adhesion of T cells to bEnd.3 cells was observed. Using western blot analysis, an increase in ICAM-1 expression was detected for both t-PA-treated bEnd.3 cells and bEnd.3 cells treated with a non-enzymatic form of t-PA. In contrast, when LRP1 was blocked using a specific antibody, upregulation of ICAM-1 was inhibited and cAMP-PKA signaling was affected. Furthermore, using an EAE mouse model, administration of t-PA was associated with an increase in ICAM-1 expression by brain endothelial cells. Taken together, these findings suggest that t-PA can induce ICAM-1 expression in brain microvascular endothelial cells, and this may promote the development of EAE.

KEYWORDS:

Endothelial cells; Experimental autoimmune encephalomyelitis; ICAM-1; LRP1; Tissue-type plasminogen activator

PMID:
24650778
DOI:
10.1016/j.clim.2014.03.004
[Indexed for MEDLINE]

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