Leukemia Research Group, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway.
Section for Hematology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
Cells. 2023 Mar 24;12(7):1003. doi: 10.3390/cells12071003.
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Common causes include gram-negative and gram-positive bacteria as well as fungi. Neutrophils are among the first cells to arrive at an infection site where they function as important effector cells of the innate immune system and as regulators of the host immune response. The regulation of neutrophil migration is therefore important both for the infection-directed host response and for the development of organ dysfunctions in sepsis. Downregulation of CXCR4/CXCL12 stimulates neutrophil migration from the bone marrow. This is followed by transmigration/extravasation across the endothelial cell barrier at the infection site; this process is directed by adhesion molecules and various chemotactic gradients created by chemotactic cytokines, lipid mediators, bacterial peptides, and peptides from damaged cells. These mechanisms of neutrophil migration are modulated by sepsis, leading to reduced neutrophil migration and even reversed migration that contributes to distant organ failure. The sepsis-induced modulation seems to differ between neutrophil subsets. Furthermore, sepsis patients should be regarded as heterogeneous because neutrophil migration will possibly be further modulated by the infecting microorganisms, antimicrobial treatment, patient age/frailty/sex, other diseases (e.g., hematological malignancies and stem cell transplantation), and the metabolic status. The present review describes molecular mechanisms involved in the regulation of neutrophil migration; how these mechanisms are altered during sepsis; and how bacteria/fungi, antimicrobial treatment, and aging/frailty/comorbidity influence the regulation of neutrophil migration.
败血症是一种危及生命的器官功能障碍,由宿主对感染的失调反应引起。常见的病因包括革兰氏阴性菌和革兰氏阳性菌以及真菌。中性粒细胞是最早到达感染部位的细胞之一,它们作为先天免疫系统的重要效应细胞和宿主免疫反应的调节剂发挥作用。因此,中性粒细胞迁移的调节对于感染导向的宿主反应和败血症中器官功能障碍的发展都很重要。CXCR4/CXCL12 的下调刺激中性粒细胞从骨髓中迁移。随后,穿过感染部位的内皮细胞屏障进行迁移/渗出;这个过程由粘附分子和趋化因子、脂质介质、细菌肽和受损细胞产生的肽形成的各种趋化梯度来指导。败血症会调节中性粒细胞迁移的这些机制,导致中性粒细胞迁移减少,甚至出现反向迁移,从而导致远处器官衰竭。败血症引起的调节似乎在中性粒细胞亚群之间存在差异。此外,败血症患者应被视为异质群体,因为感染微生物、抗菌治疗、患者年龄/虚弱/性别、其他疾病(如血液系统恶性肿瘤和干细胞移植)以及代谢状态可能会进一步调节中性粒细胞的迁移。本综述描述了调节中性粒细胞迁移的分子机制;这些机制在败血症期间如何发生改变;以及细菌/真菌、抗菌治疗和衰老/虚弱/合并症如何影响中性粒细胞迁移的调节。