Department of Life Sciences and Bioethics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.
Department of Nutrition in Cardiovascular Disease, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.
FEBS Open Bio. 2021 May;11(5):1374-1381. doi: 10.1002/2211-5463.13144. Epub 2021 Apr 3.
Leukocytes play an important role in vascular inflammation prior to atherosclerosis. In particular, monocyte adhesion and migration to the endothelium contribute to the development of vascular inflammation. Previously, we showed the importance of neutrophils and complement C5a in the early phase of vascular inflammation in mice fed a high-fat diet. However, the relationship between monocytes and neutrophils is not well understood. In this study, we elucidated the involvement of neutrophils in the migration of monocytes. We observed that C5a induces CCL2 expression in neutrophil-like dHL-60 cells. To investigate the physiological significance of CCL2 secretion, we performed a chemotaxis assay. Interestingly, dHL-60 culture supernatant in the presence of C5a enhanced the migration of THP-1 in comparison with the absence of C5a. Furthermore, CCL2 expression and secretion significantly increased in C5a-stimulated dHL-60 through the phosphorylation of NF-κB p65. Actin polymerization on THP-1 was enhanced by the presence of C5a compared with the absence of C5a when stimulated by a dHL-60-cultured medium. These results suggest that crosstalk between neutrophils and monocytes via CCL2 may play an important role in vascular inflammation.
白细胞在动脉粥样硬化前的血管炎症中起着重要作用。特别是单核细胞黏附和迁移到内皮细胞有助于血管炎症的发展。以前，我们在高脂饮食喂养的小鼠中显示了中性粒细胞和补体 C5a 在血管炎症的早期阶段的重要性。然而，单核细胞和中性粒细胞之间的关系尚不清楚。在这项研究中，我们阐明了中性粒细胞在单核细胞迁移中的作用。我们观察到 C5a 诱导类中性粒细胞 dHL-60 细胞中 CCL2 的表达。为了研究 CCL2 分泌的生理意义，我们进行了趋化性测定。有趣的是，与不存在 C5a 相比，存在 C5a 时 dHL-60 培养上清液增强了 THP-1 的迁移。此外，通过 NF-κB p65 的磷酸化，C5a 刺激的 dHL-60 中 CCL2 的表达和分泌显著增加。与不存在 C5a 相比，当用 dHL-60 培养的培养基刺激时，THP-1 上的肌动蛋白聚合增强。这些结果表明，通过 CCL2 进行的中性粒细胞和单核细胞之间的串扰可能在血管炎症中起重要作用。
