Although high level of circulating C-reactive protein (pCRP) is considered as a biomarker for disease activity, the significance of CRP in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been clarified. We once reported in AAV, pentameric CRP (pCRP) could dissociate into monomeric CRP (mCRP) and activate platelets. Recent studies have demonstrated that the activated platelets can release mitochondrial DNA (mtDNA). The purpose of this study was to further study the relationship between mCRP and platelets in AAV. We found the plasma level of mCRP in AAV patients was significantly higher than that of normal control and positively correlated with the proportion of mCRP-positive platelets. Platelets isolated from one normal donor could be activated by plasma from 5 AAV patients and this effect could be attenuated when mCRP had been removed. Only 0.1 μg/mL of recombinant mCRP was needed for inducing platelets to release mtDNA via interaction with lipid raft and through p38 MAPK/NF-κB pathway. The mCRP binding on platelets depended on the C-terminal octapeptide (aa 199–206). The released mtDNA did not induce respiratory burst alone, but enhanced the ANCA-induced neutrophils respiratory burst after binding Toll-like receptor 9 (TLR9). The mtDNA released by mCRP-activated platelets also enhanced thrombin generation of plasma. In conclusion, our data demonstrate that mCRP can bind platelets via interaction with lipid raft and induce the release of mtDNA. The released mtDNA can enhance the pathogenicity of ANCA and promote activation of coagulation system in AAV.

尽管高水平的循环 C 反应蛋白 (pCRP) 被认为是疾病活动的生物标志物，但 CRP 在抗中性粒细胞胞浆抗体 (ANCA) 相关血管炎 (AAV) 发病机制中的重要性尚未阐明。我们曾经在 AAV 中报道过，五聚体 CRP (pCRP) 可以解离成单体 CRP (mCRP) 并激活血小板。最近的研究表明，活化的血小板可以释放线粒体 DNA (mtDNA)。本研究的目的是进一步研究 AAV 中 mCRP 与血小板之间的关系。我们发现 AAV 患者血浆 mCRP 水平显着高于正常对照，并与 mCRP 阳性血小板比例呈正相关。从一名正常供体分离的血小板可以被 5 名 AAV 患者的血浆激活，当 mCRP 被去除时，这种影响会减弱。仅需要 0.1 μg/mL 的重组 mCRP 即可通过与脂筏的相互作用和 p38 MAPK/NF-κB 途径诱导血小板释放 mtDNA。mCRP 与血小板的结合取决于 C 端八肽 (aa 199-206)。释放的 mtDNA 不会单独诱导呼吸爆发，而是在结合 Toll 样受体 9 (TLR9​​) 后增强 ANCA 诱导的中性粒细胞呼吸爆发。mCRP 激活的血小板释放的 mtDNA 也增强了血浆的凝血酶生成。总之，我们的数据表明 mCRP 可以通过与脂筏的相互作用结合血小板并诱导 mtDNA 的释放。