2. Academic Validation
  3. ATP release drives heightened immune responses associated with hypertension

ATP release drives heightened immune responses associated with hypertension

  • Sci Immunol. 2019 Jun 28;4(36):eaau6426. doi: 10.1126/sciimmunol.aau6426.
Tuantuan V Zhao 1,  Yu Li 1,  Xiaoli Liu 2,  Shudong Xia 3,  Peng Shi 4,  Li Li 5,  Zexin Chen 6,  Chunyou Yin 1,  Masahiro Eriguchi 7 8,  Yayu Chen 3,  Ellen A Bernstein 7,  Jorge F Giani 7 9,  Kenneth E Bernstein 7 9,  Xiao Z Shen 10
Affiliations

Affiliations

  • 1 Department of Physiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 2 Department of Neurology, Zhejiang Hospital, Hangzhou, Zhejiang, China.
  • 3 Department of Cardiology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
  • 4 Department of Cardiology of the Second Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 5 Department of Pharmacy, Zhejiang Hospital, Hangzhou, Zhejiang, China.
  • 6 Center of Clinical Epidemiology & Biostatistics, Department of Science and Education, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 7 Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • 8 Department of Nephrology, Nara Medical University, Kashihara, Nara, Japan.
  • 9 Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • 10 Department of Physiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. shenx@zju.edu.cn.
PMID: 31253642 DOI: 10.1126/sciimmunol.aau6426
Abstract

The cause of most hypertensive disease is unclear, but inflammation appears critical in disease progression. However, how elevated blood pressure initiates inflammation is unknown, as are the effects of high blood pressure on innate and adaptive immune responses. We now report that hypertensive mice have increased T cell responses to antigenic challenge and develop more severe T cell-mediated immunopathology. A root cause for this is hypertension-induced erythrocyte adenosine 5'-triphosphate (ATP) release, leading to an increase in plasma ATP levels, which begins soon after the onset of hypertension and stimulates P2X7 receptors on antigen-presenting cells (APCs), increasing APC expression of CD86. Hydrolyzing ATP or blocking the P2X7 Receptor eliminated hypertension-induced T cell hyperactivation. In addition, pharmacologic or genetic blockade of P2X7 Receptor activity suppressed the progression of hypertension. Consistent with the results in mice, we also found that untreated human hypertensive patients have significantly elevated plasma ATP levels compared with treated hypertensive patients or normotensive controls. Thus, a hypertension-induced increase in extracellular ATP triggers augmented APC and T cell function and contributes to the immune-mediated pathologic changes associated with hypertensive disease.

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