Recognition of apoptotic cells by viable cells is specific, ubiquitous, and species independent: analysis using photonic crystal biosensors.
Recognition of apoptotic cells by viable cells is specific, ubiquitous, and species independent: analysis using photonic crystal biosensors.
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DOI：
10.1091/mbc.e13-11-0700
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发表时间：
2014-06
影响因子：
3.3
通讯作者：
Ucker DS
中科院分区：
文献类型：
--
作者：
Pattabiraman G;Lidstone EA;Palasiewicz K;Cunningham BT;Ucker DS
细胞凋亡识别与深刻的抗炎和免疫抑制反应有关。一种用于评估细胞凋亡识别的灵敏的光子晶体生物传感器方法表明，细胞凋亡识别以一种显著的物种独立的方式发生，并有专有的细胞骨架参与。细胞凋亡的识别是与生俱来的，并与一种涉及抗炎和免疫抑制反应的深刻的免疫调节(固有的凋亡免疫[IAI])有关。这种反应的许多分子和机制细节仍然难以捉摸。虽然免疫结果可以很容易地量化，但最初的特定识别事件很难评估。我们开发了一种灵敏的、实时的方法来检测存活的贴壁反应细胞对凋亡细胞的识别，使用了光子晶体生物传感器方法。该方法依赖于粘附性反应细胞与非粘附性凋亡靶点的特异性识别和剂量依赖性相互作用所产生的特征光谱移位。值得注意的是，生物传感器提供了发生在生物传感器表面远端的反应细胞中早期识别特定事件的读数。我们发现，与生俱来的凋亡细胞识别以一种显著的物种独立方式发生，这与我们之前的工作和从间接分析得出的推断一致。我们的研究表明，尽管不涉及凋亡细胞吞噬作用，但专性细胞骨架参与。由于它是识别的直接、客观和定量读数，这种生物传感器方法提供了一种方法学，可以用来剖析与IAI和免疫抑制相关的早期识别事件。
Apoptotic recognition is linked to profound anti-inflammatory and immunosuppressive responses. A sensitive photonic crystal biosensor method for the assessment of apoptotic recognition shows that apoptotic recognition occurs in a strikingly species-independent manner, with obligate cytoskeletal involvement. Apoptotic recognition is innate and linked to a profound immune regulation (innate apoptotic immunity [IAI]) involving anti-inflammatory and immunosuppressive responses. Many of the molecular and mechanistic details of this response remain elusive. Although immune outcomes can be quantified readily, the initial specific recognition events have been difficult to assess. We developed a sensitive, real-time method to detect the recognition of apoptotic cells by viable adherent responder cells, using a photonic crystal biosensor approach. The method relies on characteristic spectral shifts resulting from the specific recognition and dose-dependent interaction of adherent responder cells with nonadherent apoptotic targets. Of note, the biosensor provides a readout of early recognition-specific events in responder cells that occur distal to the biosensor surface. We find that innate apoptotic cell recognition occurs in a strikingly species-independent manner, consistent with our previous work and inferences drawn from indirect assays. Our studies indicate obligate cytoskeletal involvement, although apoptotic cell phagocytosis is not involved. Because it is a direct, objective, and quantitative readout of recognition exclusively, this biosensor approach affords a methodology with which to dissect the early recognition events associated with IAI and immunosuppression.