Ding Ziqiang, Jia Song H, Marshall John C, Downey Gregory P, Waddell Thomas K
Division of Thoracic Surgery, Department of Surgery, Toronto General Research Institute of the University Health Network, University of Toronto, Toronto, ON, Canada.
Crit Care Med. 2006 Dec;34(12):3011-7. doi: 10.1097/01.CCM.0000247719.37793.43.
Lymphocyte dysfunction has been documented in sepsis, and evidence suggests that lymphocyte infiltration contributes to tissue injury. The purpose of this study was to examine chemokine receptor expression and function in lymphocytes from septic patients and healthy donors.
Observational study of septic patients and laboratory investigation of normal controls.
Tertiary care intensive care unit.
Nine critically ill patients fulfilling criteria for the systemic inflammatory response syndrome and with a Sepsis Score of >/=3 were included in this study. Lymphocytes were also obtained from healthy volunteers.
None.
The total number of circulating leukocytes in septic patients was markedly increased; however, lymphocyte counts were decreased. Chemokine receptor expression on lymphocytes was examined by flow cytometry. CXCR4 expression on lymphocytes from septic patients was increased whereas CCR5 was decreased and CCR7 was unchanged. Lipopolysaccharide stimulation of normal lymphocytes increased CXCR4 expression but decreased CCR5 and did not change CCR7 expression. This lipopolysaccharide-stimulated CXCR4 expression required 20 hrs of stimulation and was accompanied by increased messenger RNA. Lymphocytes from septic patients or after lipopolysaccharide treatment demonstrated enhanced actin polymerization and migration in response to CXCL12. Taken together, sepsis and lipopolysaccharide up-regulated CXCR4 expression and enhanced lymphocyte activation and migration in response to CXCL12.
Blocking CXCR4 and CXCL12 function may provide a novel therapeutic method for controlling systemic inflammation and tissue injury in sepsis.
淋巴细胞功能障碍在脓毒症中已有记载，且有证据表明淋巴细胞浸润会导致组织损伤。本研究旨在检测脓毒症患者和健康供体淋巴细胞中趋化因子受体的表达及功能。
对脓毒症患者进行观察性研究，并对正常对照进行实验室检测。
三级医疗重症监护病房。
本研究纳入了9例符合全身炎症反应综合征标准且脓毒症评分≥3分的重症患者。同时也从健康志愿者中获取淋巴细胞。
无。
脓毒症患者循环白细胞总数显著增加；然而，淋巴细胞计数减少。通过流式细胞术检测淋巴细胞上趋化因子受体的表达。脓毒症患者淋巴细胞上CXCR4的表达增加，而CCR5减少，CCR7不变。用脂多糖刺激正常淋巴细胞会增加CXCR4的表达，但会降低CCR5，且不改变CCR7的表达。这种脂多糖刺激的CXCR4表达需要20小时的刺激，并伴随着信使核糖核酸的增加。脓毒症患者的淋巴细胞或经脂多糖处理后的淋巴细胞对CXCL12的反应表现为肌动蛋白聚合增强和迁移增强。综上所述，脓毒症和脂多糖上调了CXCR4的表达，并增强了淋巴细胞对CXCL12的激活和迁移反应。
阻断CXCR4和CXCL12的功能可能为控制脓毒症中的全身炎症和组织损伤提供一种新的治疗方法。
