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

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

  • Clin Immunol. 2014 May-Jun;152(1-2):90-100. doi: 10.1016/j.clim.2014.03.004.
Jinghua Wang 1,  Xin Zhang 2,  Lili Mu 1,  Mingqing Zhang 1,  Zhongming Gao 1,  Jia Zhang 1,  Xiuhua Yao 1,  Chuanliang Liu 1,  Guangyou Wang 1,  Dandan Wang 1,  Qingfei Kong 1,  Yumei Liu 1,  Na Li 1,  Bo Sun 3,  Hulun Li 4
Affiliations

Affiliations

  • 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.
PMID: 24650778 DOI: 10.1016/j.clim.2014.03.004
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.

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