严重损伤后人中性粒细胞中，肿瘤坏死因子-α 黏附依赖性过氧化物生成的CXCR2调节作用显著减弱。

CXCR2 regulation of tumor necrosis factor-alpha adherence-dependent peroxide production is significantly diminished after severe injury in human neutrophils.

作者信息

Quaid G, Williams M, Cave C, Solomkin J

机构信息

Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0558, USA.

出版信息

J Trauma. 2001 Sep;51(3):446-51. doi: 10.1097/00005373-200109000-00004.

DOI:10.1097/00005373-200109000-00004

PMID:11535888

Abstract

BACKGROUND

Primed neutrophils are thought to play a key role in inflammatory pathology. We have shown though in vitro studies that interleukin (IL)-8 and growth-related oncogene-alpha (GROalpha) (CXCR2-specific chemokines) regulate the respiratory burst via the CXCR2 receptor. We have also shown in vivo, CXCR2 receptors are down-regulated in severely injured patients. Our hypothesis is that regulation of the respiratory burst by CXCR2 is lost after severe injury.

METHODS

Patient neutrophils were studied within 24 hours of admission to the hospital; excluded were severe head injury and patients with Injury Severity Score < 16. Patient and normal neutrophils were isolated by Ficoll-Hypaque centrifugation after dextran sedimentation. Neutrophils were plated with buffer, 50 nmol/L IL-8 or GROalpha on fibronectin-coated plates for 15 minutes, then stimulated with 10 ng/mL of TNFalpha. CXCR2 expression was measured by flow cytometry. Receptor function was assessed by calcium mobilization.

RESULTS

One female and 10 male patients with an average age of 37 +/- 3 and Injury Severity Score of 24 +/- 5 suffered blunt injury. CXCR2 showed a 32% +/- 7% loss, whereas CXCR1 showed 15% +/- 6% reduction. GROalpha stimulation of patient neutrophils showed 60% +/- 16% decrease in calcium mobilization, whereas IL-8 showed no decline. At 40 minutes, IL-8 and GROalpha significantly inhibited TNFalpha adherence-dependent peroxide production in normal neutrophils (35% +/- 4% and 45% +/- 3%, respectively; p < 0.05). Both IL-8 and GROalpha lost the ability to suppress the respiratory burst in severely injured patients, but GROalpha had a significantly greater loss of this suppression (p = 0.004).

CONCLUSION

IL-8 and GROalpha lose the ability to regulate the TNFalpha-induced respiratory burst. This may contribute to neutrophil dysregulation after injury and result in organ injury.

摘要

背景

预激活的中性粒细胞被认为在炎症病理学中起关键作用。然而，我们通过体外研究表明，白细胞介素（IL）-8和生长相关癌基因α（GROα）（CXCR2特异性趋化因子）通过CXCR2受体调节呼吸爆发。我们还在体内研究中表明，严重受伤患者的CXCR2受体下调。我们的假设是，严重损伤后CXCR2对呼吸爆发的调节作用丧失。

方法

在患者入院后24小时内对其中性粒细胞进行研究；排除严重颅脑损伤患者和损伤严重度评分<16的患者。经葡聚糖沉淀后，通过Ficoll-Hypaque离心法分离患者和正常中性粒细胞。将中性粒细胞接种于纤连蛋白包被的培养板上，分别加入缓冲液、50 nmol/L IL-8或GROα，孵育15分钟，然后用10 ng/mL肿瘤坏死因子α（TNFα）刺激。通过流式细胞术检测CXCR2表达。通过钙动员评估受体功能。

结果

1例女性和10例男性患者，平均年龄37±3岁，损伤严重度评分为24±5分，均为钝性损伤。CXCR2表达下降32%±7%，而CXCR1表达下降15%±6%。GROα刺激患者中性粒细胞后，钙动员减少60%±16%，而IL-8刺激后无下降。40分钟时，IL-8和GROα显著抑制正常中性粒细胞中TNFα依赖黏附的过氧化物产生（分别为35%±4%和45%±3%；p<0.05）。IL-8和GROα均丧失了抑制严重受伤患者呼吸爆发的能力，但GROα这种抑制能力的丧失更为显著（p = 0.004）。