Department of Pharmacology, School of Medicine of Ribeirão Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
Department of CRID: Center for Research in Inflammatory Diseases, School of Medicine of Ribeirão Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
Shock. 2019 Nov;52(5):e100-e106. doi: 10.1097/SHK.0000000000001301.
Neutrophils and inflammatory monocytes control sepsis by migration to the site of infection via their chemokine receptors. CCR5 is a chemokine receptor that is not expressed on neutrophils and inflammatory monocytes under homeostatic conditions. However, it has been demonstrated that CCR5 can become expressed on these cells during different models of inflammation. In the present study, we investigated if CCR5 is also expressed on neutrophil and inflammatory monocytes during sepsis, exerting an important role in the migration of these cells to the infectious focus. Using cecal ligation and puncture model to induce polymicrobial sepsis, we demonstrated that the expression of CCR5 is induced on CD11bLy6GLy6C inflammatory monocytes, but not on neutrophils (CD11bLy6GLy6C). Furthermore, CCR5 plays an important role for the migration of the inflammatory monocytes to infection focus during sepsis. CCR5-expressing inflammatory monocytes migrate from the bone marrow to the circulation and then into the site of infection, where they phagocytize and kill the bacteria. Consequently, CCR5 mice showed increased systemic inflammatory response and mortality compared to wild-type mice. These data therefore demonstrate a hitherto unrecognized protective role of CCR5 in sepsis.
中性粒细胞和炎性单核细胞通过趋化因子受体向感染部位迁移来控制败血症。CCR5 是一种趋化因子受体，在稳态条件下，中性粒细胞和炎性单核细胞不表达 CCR5。然而，已经证明在不同的炎症模型中，CCR5 可以在这些细胞上表达。在本研究中，我们研究了 CCR5 是否也在败血症期间表达于中性粒细胞和炎性单核细胞上，在这些细胞向感染灶迁移中发挥重要作用。使用盲肠结扎和穿刺模型诱导多微生物败血症，我们证明 CCR5 在 CD11bLy6GLy6C 炎性单核细胞上表达，但不在中性粒细胞（CD11bLy6GLy6C）上表达。此外，CCR5 在败血症期间炎性单核细胞向感染灶迁移中发挥重要作用。表达 CCR5 的炎性单核细胞从骨髓迁移到循环系统，然后进入感染部位，在那里吞噬并杀死细菌。因此，与野生型小鼠相比，CCR5 敲除小鼠表现出更高的全身炎症反应和死亡率。这些数据因此表明 CCR5 在败血症中具有以前未被认识到的保护作用。
