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.

中文翻译：

---

坎格雷洛通过抑制小鼠的血小板活化来减轻博来霉素诱导的肺纤维化。

肺纤维化是一种进行性慢性炎症性肺疾病，其发病机理复杂。血小板和中性粒细胞在肺部炎症的进展中起重要作用。我们已经报道过，非特异性GPR17拮抗剂cangrelor可以通过抑制小鼠巨噬细胞炎症来部分缓解肺纤维化。坎格雷洛也是一种著名的抗血小板药。为了测试坎格雷洛是否部分通过抑制血小板来减轻肺纤维化，使用博来霉素（BLM）诱导C57BL / 6 J小鼠肺纤维化。我们发现坎格雷洛（10 mg / kg）不仅显着降低了BLM诱导的炎性细胞因子（PF4，CD40 L和MPO）的释放，还降低了血小板的增量，BLM治疗的小鼠的纤维化肺和外周血中性粒细胞和血小板中性粒细胞聚集。此外，坎格雷洛降低了BLM处理的小鼠肺中CD40和MPO双阳性中性粒细胞的数量以及CD40的表达水平。根据这些结果，我们得出结论，坎格雷洛可以部分抑制血小板活化，从而减轻BLM诱导的小鼠肺部炎症和肺纤维化，从而减少由于CD40-CD40 L相互作用介导的血小板和中性粒细胞的粘附而引起的中性粒细胞的浸润。Cangrelor可能是治疗肺纤维化的潜在药物。根据这些结果，我们得出结论，坎格雷洛可以部分抑制血小板活化，从而减轻BLM诱导的小鼠肺部炎症和肺纤维化，从而减少由于CD40-CD40 L相互作用介导的血小板和中性粒细胞的粘附而引起的中性粒细胞的浸润。Cangrelor可能是治疗肺纤维化的潜在药物。根据这些结果，我们得出结论，坎格雷洛可以部分抑制血小板活化，从而减轻BLM诱导的小鼠肺部炎症和肺纤维化，从而减少由于CD40-CD40 L相互作用介导的血小板和嗜中性粒细胞的粘附而引起的嗜中性粒细胞的浸润。Cangrelor可能是治疗肺纤维化的潜在药物。