Folic acid targets splenic extramedullary hemopoiesis to attenuate carbon black-induced coagulation-thrombosis potential
Folic acid targets splenic extramedullary hemopoiesis to attenuate carbon black-induced coagulation-thrombosis potential
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DOI：
10.1016/j.jhazmat.2021.127354
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发表时间：
2021-10-09
影响因子：
13.6
通讯作者：
Chen, Rui
中科院分区：
文献类型：
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作者：
Meng, Qingtao;Li, Bin;Chen, Rui
由于炭黑 (CB) 在轮胎和橡胶产品中的广泛应用，其生产、收集和处理过程中的安全性受到关注。在这里，我们报告暴露 CB，以脾髓外造血 (EMH) 依赖性方式增加凝血血栓形成潜力。成年 C57BL/6 小鼠被饲养在全身吸入室中，并连续 28 天暴露于过滤的室内空气 (FRA) 或 CB。 CB暴露导致脾EMH，其特征为血小板前体细胞、巨核细胞(MK)、增生和体内凝血能力增强。代谢组学分析表明，接触 CB 后，小鼠血清中 PGE2 的产生显着增加，但叶酸 (FA) 水平降低。从机制上讲，COX 依赖性 PGE2 产生的激活会促进脾巨噬细胞中 IL-6 的表达，从而导致脾 EMH 和循环中血小板计数增加。 FA通过抑制脾巨噬细胞中前列腺素内过氧化物合酶2（Ptgs2或Cox2）和前列腺素E合酶（Ptges）的表达来保护小鼠免受CB诱导的脾EMH，最终使凝血能力恢复到正常水平。结果强烈表明，脾 EMH 参与了对 CB 暴露的反应，并随后增加了凝血-血栓形成的可能性。补充 FA 可能是预防由于 CB 暴露而导致血栓形成的候选者。
Due to its wide applications in tire and rubber products, carbon black (CB) implicates concerns on its safety during production, collection, and handling. Here we report that exposure CB, increases coagulation-thrombosis potential in a splenic extramedullary hemopoiesis (EMH)-dependent manner. Adult C57BL/6 mice are kept in whole-body inhalation chambers, and exposed to filtered room air (FRA) or CB for 28 consecutive days. CB exposure resulted in splenic EMH characterized with platelet precursor cells, megakaryocytes (MKs), hyperplasia and enhanced in vivo blood coagulation ability. Metabolomics analysis suggests significant enhance in PGE2 production but reduction in folic acid (FA) levels in murine serum following CB exposure. Mechanistically, activation of COX-dependent PGE2 production promotes IL-6 expression in splenic macrophages, which subsequently results in splenic EMH and increased platelet counts in circulation. Administration of FA protects the mice against CB-induced splenic EMH through inhibiting prostaglandin-endoperoxide synthase 2 (Ptgs2 or Cox2) and prostaglandin E synthase (Ptges) expression in splenic macrophages, eventually recover the coagulation capacity to normal level. The results strongly suggest the involvement of splenic EMH in response to CB exposure and subsequently increased coagulation-thrombosis potential. Supplementation with FA may be a candidate to prevent thrombosis potential attributable to CB exposure.