免疫细胞的内部指南针

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加州大学圣地亚哥分校医学院的研究人员发现了嗜中性球如何朝着受到感染和发炎的部位移动。嗜中性球是一种专化的白血球，在身体对抗发炎及细菌感染的机制中扮演着重要的角色。这项研究结果将有助于引导出有效的重度感染和发炎性疾病之新疗法。

这项研究报告发表于12月15 日的Science中，研究描述嗜中性球用于侦测细菌和发炎组织的内部指南针。研究结果解决了科学家长久以来所面临的难题，嗜中性球如何寻找并朝着身体的感染部位前进。他们发现嗜中性会借着内部指南针朝着化学吸引因子（chemoattractants）移动，化学吸引因子是由细菌或感染部位所释放出的。

研究人员发现，嗜中性球具有一个放大系统可瞄准化学吸引因子，而这套放大系统的核心正是三磷酸腺苷adenosine triphosphate (ATP)。引起嗜中性球移动的事件链先从接近化学吸引因子的区域释放出ATP开始，ATP会与嗜中性球表面P2Y2受体结合，使嗜中性球定位化学吸引因子的来源。一旦内部指南针启动，ATP被细胞转换成adenosine，反过来启动A3 adenosine受体，提供朝向化学吸引因子移动的信号。

研究人员抑制ATP受体后，发现嗜中性球迷失了方向，而阻拦A3 adenosine受体时，减缓了嗜中性球移动至化学吸引因子的速度。研究人员也发现，影响放大作用系统的药物，会减弱细胞移动至发炎组织的能力。

这些研究结果非常重要，因为它们指引出研发抗发炎药物的目标，同时也可以进一步研发出治疗慢性发炎性疾病如气喘、类风湿性关节炎等的疗法。

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Process by which neutrophils detect and migrate towards chemoattractants. Credit: UCSD Medical Center Researchers at the University of California, San Diego (UCSD) School of Medicine have discovered how neutrophils – specialized white blood cells that play key roles in inflammation and in the body's immune defense against bacteria – navigate to sites of infection and inflammation. These findings could potentially lead to new treatments for serious infections and inflammatory diseases in patients.
The research, reported in the December 15, 2006 issue of the journal Science, describes the elements of the "internal compass" that neutrophils use to detect and migrate towards chemoattractants, markers of infection and inflammation that are released from bacteria and inflamed tissues.
"These findings solve the long-standing puzzle of how neutrophils find their way and move toward sites of injury or infection in the body," said senior author Wolfgang Junger, Ph.D., adjunct professor of surgery at UCSD Medical Center.
His team set out to identify the key mechanisms of signal amplification that must occur in order for neutrophils to detect the low-level activating signals (chemoattractants) sent out by bacteria at injury sites. They found that neutrophils possess a built-in amplification system that is an integral part of the internal compass the cells use to locate the source of chemoattractants. At the core of the amplification system is the chemical adenosine triphosphate (ATP).
The chain of events necessary to direct the neutrophils toward its goal begins when ATP is released from the region of the cell surface closest to the source of chemoattractants. Next, ATP binds to a nucleotide receptor called P2Y2 on the cell surface, a step critical to position the cells in the direction of the source of chemoattractants.
Once this internal compass has been activated, ATP is converted by the cells to adenosine, which in turn activates A3 adenosine receptors concentrated at the front of cells, providing the signal to move toward the source of chemoattractants.
Lead authors Yu Chen, M.D., UCSD postgraduate researcher in surgery and Ross Corriden, UCSD graduate student in biomedical sciences, found that when ATP receptors were blocked, the cells became disoriented, while blocking A3 adenosine receptors slowed down the cell movement toward chemoattractants. The researchers also found that drugs which interfere with the amplification system impair cell migration to inflamed tissues.
"These findings are very important because they suggest that novel classes of anti-inflammatory drugs could be developed to prevent rheumatoid arthritis, inflammatory bowel diseases, asthma, and many other chronic inflammatory diseases," said Junger.
Conversely, drugs that boost these amplification systems and the internal compass could be used to coax neutrophils to migrate to infected wounds to improve wound healing.