图片来源:PNAS(DOI:https://doi.org/10.1073/pnas.1720553115)
论文的通讯作者Éric Boilard教授说:“当一个外来物首次进入血液时,它会导致抗体的产生。当这些抗体下次遇到相同的外来物,会快速附着在其表面,形成抗原-抗体复合物,触发炎症反应。而血小板具有能够识别这些复合物的受体FcγRIIA。这就是为什么,我们会怀疑血小板参与了炎症过程。”
为了验证这样的假设,研究者们利用一种病毒、一种细菌毒素和一种引发过敏的蛋白,在正常小鼠的血液中制造了抗原-抗体复合物。所有这3种情况下,结果都是相似的:小鼠表现出了典型的败血性或过敏性休克的症状,也就是,体温下降、震颤、心脏功能受损、血管扩张以及意识丧失。
图片来源:网络
接着,科学家们在“几乎所有血小板都被移除的小鼠”和“血小板上没有抗原-抗体复合物受体的小鼠”中重复了以上测试。结果显示,这些小鼠没有生理响应,这清楚地说明了血小板在其中起到的关键作用。
研究发现,实验中,正常的小鼠之所以休克,是因为其血小板释放了血清素(serotonin)。该物质是和大脑中的神经递质相同的分子。血小板储存了血清素,并在特定的情况下将其释放出来。
在论文的Significance板块,作者们总结道,该研究证实,循环的抗原-抗体复合物会通过激活FcγRIIA诱导休克,而这种休克实际上由血清素的释放所介导的。在对循环抗原-抗体复合物的响应中,血小板是“与败血症、病毒血症和过敏性反应高度相关的炎性反应”的关键调节者。
该研究的一个临床意义是,证明了对败血性或过敏性休克患者进行血小板输注,可能会通过增加血液中血清素的含量,使患者病情加重。Boilard教授说:“为了预防这一问题发生,在某些情况下,血小板上的抗原-抗体复合物受体可能需要事先被阻断。”
参考资料:
Researchers discover the unexpected role of platelets in immune response
There is a growing appreciation for the contribution of platelets to immunity; however, our knowledge mostly relies on platelet functions associated with vascular injury and the prevention of bleeding. Circulating immune complexes (ICs) contribute to both chronic and acute inflammation in a multitude of clinical conditions. Herein, we scrutinized platelet responses to systemic ICs in the absence of tissue and endothelial wall injury. Platelet activation by circulating ICs through a mechanism requiring expression of platelet Fcγ receptor IIA resulted in the induction of systemic shock. IC-driven shock was dependent on release of serotonin from platelet-dense granules secondary to platelet outside-in signaling by αIIbβ3 and its ligand fibrinogen. While activated platelets sequestered in the lungs and leaky vasculature of the blood–brain barrier, platelets also sequestered in the absence of shock in mice lacking peripheral serotonin. Unexpectedly, platelets returned to the blood circulation with emptied granules and were thereby ineffective at promoting subsequent systemic shock, although they still underwent sequestration. We propose that in response to circulating ICs, platelets are a crucial mediator of the inflammatory response highly relevant to sepsis, viremia, and anaphylaxis. In addition, platelets recirculate after degranulation and sequestration, demonstrating that in adaptive immunity implicating antibody responses, activated platelets are longer lived than anticipated and may explain platelet count fluctuations in IC-driven diseases.
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