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脓毒症和严重全身性炎症反应综合征患者不成熟中性粒细胞的固有免疫功能。

Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response syndrome.

机构信息

Laboratory of Intensive Care, University Hospitals of Geneva, University of Geneva, Switzerland.

出版信息

Crit Care Med. 2013 Mar;41(3):820-32. doi: 10.1097/CCM.0b013e318274647d.

DOI:10.1097/CCM.0b013e318274647d
PMID:23348516
Abstract

OBJECTIVE

A hallmark of sepsis and severe systemic inflammatory response syndrome (SIRS) is the massive recruitment of immature neutrophils from the bone marrow into the circulation (left shift, band forms). Their capacity to participate in innate defense against bacteria is ill defined. We aimed at comparing various innate immune functions of mature vs. immature neutrophils circulating during sepsis and SIRS.

DESIGN

Prospective, observational cohort study.

SETTING

Tertiary level ICU and associated research laboratory.

PATIENTS

: Thirty-three ICU patients with sepsis; 12 ICUs with SIRS; 32 healthy volunteers.

INTERVENTIONS

Twenty milliliters of whole heparinized blood was used for in vitro studies including neutrophil viability and apoptosis, surface expression of CD16, Toll-like receptors () 4 and TLR2, CD14, MD-2, HLA-DP,-DQ and -DR, and CXCR2, chemotaxis, phagocytosis, bacterial killing, and tumor necrosis factor-α/interleukin-10 baseline intracellular cytokine levels.

MEASUREMENTS AND MAIN RESULTS

Immature neutrophils were capable of mediating important innate immune functions such as bacterial phagocytosis and killing via the production of reactive oxygen species, although less efficiently than mature neutrophils. Immature neutrophils had a longer life span and resistance to spontaneous apoptosis, and could mature ex vivo. They expressed lower levels of receptors for bacterial molecules such as CD14 and MD-2 and migrated less efficiently than mature granulocytes. Immature neutrophils had higher basal intracellular tumor necrosis factor-α/interleukin-10 ratio than that of mature neutrophils, suggesting a proinflammatory phenotype. No significant differences were observed between immature neutrophils isolated from patients with sepsis and those from patients with severe SIRS.

CONCLUSIONS

Despite their "immaturity", band forms are capable of mediating crucial innate immune functions during severe infections and sepsis. Their fate and capacity to mature in vivo remain to be determined.

摘要

目的

脓毒症和严重全身炎症反应综合征(SIRS)的一个标志是大量未成熟中性粒细胞从骨髓募集到循环中(左移,带状形成)。它们参与针对细菌的固有防御的能力尚未明确。我们旨在比较脓毒症和 SIRS 期间循环中成熟与未成熟中性粒细胞的各种固有免疫功能。

设计

前瞻性观察队列研究。

地点

三级 ICU 及相关研究实验室。

患者

33 例 ICU 脓毒症患者;12 例 SIRS 患者;32 名健康志愿者。

干预措施

使用 20 毫升肝素化全血进行体外研究,包括中性粒细胞活力和凋亡、CD16、Toll 样受体(TLR)4 和 TLR2、CD14、MD-2、HLA-DP、-DQ 和 -DR、CXCR2、趋化性、吞噬作用、细菌杀伤和肿瘤坏死因子-α/白细胞介素-10 基础细胞内细胞因子水平。

测量和主要结果

未成熟中性粒细胞能够通过产生活性氧物质介导重要的固有免疫功能,如细菌吞噬和杀伤,尽管效率低于成熟中性粒细胞。未成熟中性粒细胞寿命更长,对自发凋亡的抵抗力更强,并且可以在体外成熟。它们表达的细菌分子受体(如 CD14 和 MD-2)水平较低,迁移效率低于成熟粒细胞。未成熟中性粒细胞的基础细胞内肿瘤坏死因子-α/白细胞介素-10 比值高于成熟中性粒细胞,提示其具有促炎表型。从脓毒症患者和严重 SIRS 患者中分离出的未成熟中性粒细胞之间未观察到显著差异。

结论

尽管处于“不成熟”状态,但带状形式仍能够在严重感染和脓毒症期间介导关键的固有免疫功能。它们在体内的命运和成熟能力仍有待确定。

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