Knowlton Anne A
Cardiovascular Division, Department of Medicine, Molecular and Cellular Cardiology, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA.
Department of Pharmacology, University of California, Davis, CA, USA.
Adv Exp Med Biol. 2017;1003:17-34. doi: 10.1007/978-3-319-57613-8_2.
The cardiac myocyte differs strikingly from the specialized cells of the immune system, which has two different responses to invading organisms and tissue damage. Adaptive or acquired immunity generates highly specific antibodies in response to threats and is an essential component of immunity; however, adaptive immunity can take 4-7 days to mobilize, and a more primitive response, innate immunity, fills the gap. Innate immunity is expressed in complex and in primitive life forms. Specialized receptors, Toll-like receptors (TLRs), which are widely distributed throughout different tissues recognize danger signals and rapidly respond with the release of noxious substances, such as TNFα. The problem is that many endogenous molecules have been found to act as ligands for specific TLRs, and when these molecules are released into the extracellular environment, they can cause problems by activating innate immunity and an inflammatory response. In cardiac myocytes heat shock protein (HSP)60 can activate TLR4, as can HMGB1, and this type of response can amplify the response to ischemia/reperfusion leading to increased cell and tissue injury. Activation of TLRs can potentially amplify chronic, inflammatory diseases, such as ischemic heart failure. Thus, it is important to understand the regulation of the TLRs and their downstream effects. This chapter will focus on the TLRs and cardiac myocytes.
心肌细胞与免疫系统的特化细胞显著不同，免疫系统对入侵生物体和组织损伤有两种不同反应。适应性或获得性免疫会针对威胁产生高度特异性抗体，是免疫的重要组成部分；然而，适应性免疫可能需要4至7天才能动员起来，一种更原始的反应——固有免疫则填补了这一空白。固有免疫在复杂和原始生命形式中均有表达。一种广泛分布于不同组织的特殊受体——Toll样受体（TLR），能够识别危险信号，并通过释放有害物质（如肿瘤坏死因子α）迅速做出反应。问题在于，人们发现许多内源性分子可作为特定TLR的配体，当这些分子释放到细胞外环境中时，它们可通过激活固有免疫和炎症反应而引发问题。在心肌细胞中，热休克蛋白（HSP）60和高迁移率族蛋白B1（HMGB1）均可激活TLR4，这种反应类型可放大对缺血/再灌注的反应，导致细胞和组织损伤增加。TLR的激活可能会加剧慢性炎症性疾病，如缺血性心力衰竭。因此，了解TLR的调控及其下游效应非常重要。本章将重点讨论TLR与心肌细胞。
