1. Academic Validation
  2. Cangrelor alleviates bleomycin-induced pulmonary fibrosis by inhibiting platelet activation in mice

Cangrelor alleviates bleomycin-induced pulmonary fibrosis by inhibiting platelet activation in mice

  • Mol Immunol. 2020 Apr;120:83-92. doi: 10.1016/j.molimm.2020.01.017.
Tianwei Zhan 1 Taofeng Wei 2 Lingjun Dong 1 Qi Wang 1 Zixiang Wu 1 Qihang Yan 1 Weiping Zhang 2 Yunbi Lu 2 Ming Wu 3
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, the Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jie-Fang Road, Hangzhou, Zhejiang, 310009, China.
  • 2 Department of Pharmacology, Zhejiang University School of Medicine, 866 Yu-Hang-Tang Road, Hangzhou, Zhejiang, 310058, China.
  • 3 Department of Thoracic Surgery, the Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jie-Fang Road, Hangzhou, Zhejiang, 310009, China. Electronic address: iwuming22@zju.edu.cn.
Abstract

Pulmonary fibrosis is a progressive chronic inflammatory lung disease whose pathogenesis is complicated. Platelets and neutrophils play important roles in the progression of pulmonary inflammation. We have reported that cangrelor, a non-sepesific GPR17 antagonist, alleviates pulmonary fibrosis partly by inhibiting macrophage inflammation in mice. Cangrelor is also a well-known anti-platelet agent. To test whether cangrelor mitigated pulmonary fibrosis partly through the inhibition of platelets, bleomycin (BLM) was used to induce pulmonary fibrosis in C57BL/6 J mice. We found that cangrelor (10 mg/kg) not only significantly decreased BLM-induced release of inflammatory cytokines (PF4, CD40 L and MPO), but also decreased the increment of platelets, neutrophils and platelet-neutrophil aggregates in the fibrotic lung and in the peripheral blood of BLM-treated mice. In addition, cangrelor decreased the number of CD40 and MPO double positive neutrophils and the expression level of CD40 in BLM-treated mouse lungs. Based on these results we conclude that cangrelor alleviates BLM-induced lung inflammation and pulmonary fibrosis in mice, partly through inhibition of platelet activation, therefore reducing the infiltration of neutrophils due to the adhesion of platelets and neutrophils mediated by CD40 - CD40 L interaction. Cangrelor could be a potential therapeutic medicine for pulmonary fibrosis.

Keywords

Cangrelor; Inflammatory cytokines; Neutrophils; Platelets; Pulmonary fibrosis.

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