G-protein receptor responses in trauma neutrophils.
G-protein receptor responses in trauma neutrophils.
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DOI：
10.1097/00005373-200012000-00020
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发表时间：
2000-12
期刊：
影响因子：
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通讯作者：
J. Adams;C. Hauser;Z. Fekete;D. Livingston;E. Deitch
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文献类型：
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作者：
J. Adams;C. Hauser;Z. Fekete;D. Livingston;E. Deitch
创伤调节多形核中性粒细胞（PMN）功能，易导致器官衰竭和感染。损伤释放的许多化学引诱物通过G蛋白偶联（GPC）受体激活PMN，其升高PMN胞浆钙（[Ca 2 +]i）。尽管如此，损伤后中性粒细胞GPC受体的功能尚未研究。方法：11例严重创伤患者（损伤严重度评分= 31 +/- 3，8例男性和3例女性，年龄= 38 +/- 3）在损伤后第1、3和7天获得PMN。9人出现器官衰竭，1人死亡。将PMN暴露于白细胞介素-8（IL-8）、生长调节癌基因-α（GRO-α）和血小板活化因子（PAF），以刺激CXCR 1、CXCR 2和PAF受体。[Ca2+]i通量测量用于定量受体应答。在损伤后一周内研究了对单个以及系列GPC激动剂的受体应答，并与来自健康志愿者（n = 10-23）的PMN的应答进行比较。结果通过单因素方差分析、配对和非配对t检验进行评价。结果伤后早期对GRO-α和PAF的反应明显降低（P < 0.01）。对所测试的所有激动剂的反应倾向于在第1天最低，在第3天达到峰值，并且到第7天再次降低，但是对GRO-α的反应的变化最显著（p < 0.03，方差分析）。在正常PMN中，GRO-α启动IL-8，IL-8启动PAF，而在创伤PMN中，GRO-α矛盾地抑制IL-8反应，IL-8抑制PAF反应。PAF引发的IL-8反应不受损伤的影响。结论：创伤后早期对GPC激动剂的受体反应受到抑制，但到第3天时增加。正常的趋化因子引发的PMN钙动员被逆转损伤;引发的PAF是完整的。PMN GPC响应取决于激动剂遇到的顺序。损伤似乎改变了这些相互作用，从而启动了PMN功能的某些方面，同时抑制了其他方面。
BACKGROUND Trauma modulates polymorphonuclear neutrophil (PMN) function, predisposing to organ failure and infection. Many chemoattractants released by injury activate PMNs via G-protein-coupled (GPC) receptors, which elevate PMN cytosolic calcium ([Ca2+]i). Nonetheless, PMN GPC receptor function after injury is unstudied. METHODS PMNs from 11 major trauma patients (Injury Severity Score = 31 +/- 3, eight men and three women, age = 38 +/- 3) were obtained on days 1, 3, and 7 after injury. Nine developed organ failure and one died. PMNs were exposed to interleukin-8 (IL-8), growth regulated oncogene-alpha (GRO-alpha), and platelet-activating factor (PAF) to stimulate the CXCR1, CXCR2, and PAF receptors. [Ca2+]i flux measurements were used to quantify receptor responses. Receptor responses to individual as well as serial GPC agonists were studied over the week after injury and compared with the responses of PMNs from healthy volunteers (n = 10-23). Results were evaluated by one-way analysis of variance, and paired and unpaired t tests. RESULTS Responses to GRO-alpha and PAF were significantly depressed early after injury (p < 0.01). Responses to all agonists tested tended to be lowest on day 1, to peak on day 3, and to decrease again by day 7, but variations in response to GRO-alpha were the most marked (p < 0.03, analysis of variance). Whereas GRO-alpha primed IL-8 and IL-8 primed PAF in normal PMNs, GRO-alpha paradoxically suppressed IL-8 responses and IL-8 suppressed PAF responses in trauma PMNs. PAF priming of IL-8 responses was unaffected by injury. CONCLUSION Receptor responses to individual GPC agonists are suppressed early after trauma, but increase by day 3. Normal chemokine priming of PMN calcium mobilization is reversed by injury; priming by PAF is intact. PMN GPC responses depend on the sequence in which agonists are encountered. Injury appears to alter these interactions, thus priming some aspects of PMN function while simultaneously suppressing others.