Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA.
Vascul Pharmacol. 2010 Jan-Feb;52(1-2):27-36. doi: 10.1016/j.vph.2009.12.004. Epub 2009 Dec 21.
The role of the immune system is to recognize pathogens, tumor cells or dead cells and to react with a very specific and localized response. By taking advantage of a highly sophisticated system of chemokines and chemokine receptors, leukocytes such as neutrophils, macrophages, and T-lymphocytes are targeted to the precise location of inflammation. While this is a beneficial process for acute infection and inflammation, recruitment of immune cells to sites of chronic inflammation can be detrimental. It is becoming clear that these inflammatory cells play a significant role in the initiation and progression of metabolic disorders such as atherosclerosis and insulin resistance by infiltrating the artery wall and adipose tissue (AT), respectively. Data from human studies indicate that elevated plasma levels of chemokines are correlated with these metabolic diseases. Recruitment of macrophages to the artery wall is well known to be one of the first steps in early atherosclerotic lesion formation. Likewise, recruitment of macrophages to AT is thought to contribute to insulin resistance associated with obesity. Based on this knowledge, much recent work in these areas has focused on the role of chemokines in attracting immune cells (monocytes/macrophages in particular) to these 2 sites. Thus, understanding the potential for chemokines to contribute to metabolic disease can help direct studies of chemokines as therapeutic targets. In this article, we will review current literature regarding the role of chemokines in atherosclerosis and obesity-related insulin resistance. We will focus on novel work showing that chemokine secretion from endothelial cells, platelets, and adipocytes can contribute to immune cell recruitment, with a diagram showing the time course of chemokine expression and leukocyte recruitment to AT. We will also highlight a few of the less-commonly known chemokine-chemokine receptor pairs. Finally, we will discuss the potential for chemokines as therapeutic targets for treatment of atherosclerosis and insulin resistance.
免疫系统的作用是识别病原体、肿瘤细胞或死亡细胞，并做出非常特异性和局部性的反应。利用趋化因子和趋化因子受体这一高度复杂的系统，白细胞（如中性粒细胞、巨噬细胞和 T 淋巴细胞）被靶向到炎症的确切位置。虽然这对于急性感染和炎症是有益的过程，但免疫细胞募集到慢性炎症部位可能会产生不利影响。越来越明显的是，这些炎症细胞通过浸润动脉壁和脂肪组织（AT），分别在动脉粥样硬化和胰岛素抵抗等代谢紊乱的起始和进展中发挥重要作用。来自人类研究的数据表明，趋化因子的血浆水平升高与这些代谢疾病相关。众所周知，巨噬细胞向动脉壁的募集是早期动脉粥样硬化病变形成的第一步之一。同样，巨噬细胞向 AT 的募集被认为与肥胖相关的胰岛素抵抗有关。基于这一知识，这些领域的许多最新研究都集中在趋化因子在吸引免疫细胞（特别是单核细胞/巨噬细胞）到这两个部位的作用上。因此，了解趋化因子在代谢疾病中的潜在作用有助于指导针对趋化因子作为治疗靶点的研究。在本文中，我们将回顾有关趋化因子在动脉粥样硬化和肥胖相关胰岛素抵抗中的作用的现有文献。我们将重点介绍新的研究工作，表明内皮细胞、血小板和脂肪细胞分泌的趋化因子可以促进免疫细胞的募集，并展示趋化因子表达和白细胞募集到 AT 的时间过程的图表。我们还将突出介绍一些不太为人知的趋化因子-趋化因子受体对。最后，我们将讨论趋化因子作为治疗动脉粥样硬化和胰岛素抵抗的治疗靶点的潜力。
Vascul Pharmacol. 2009-12-21
Arterioscler Thromb Vasc Biol. 2014-1-16
Curr Opin Lipidol. 2010-6
J Innate Immun. 2018-4-18
Curr Pharm Des. 2012
Arterioscler Thromb Vasc Biol. 2005-12
Obes Rev. 2015-2
J Mol Med (Berl). 2008-7
Cardiovasc Res. 2009-12-9
J Ovarian Res. 2024-12-19
Plast Reconstr Surg Glob Open. 2024-3-21
Metabolites. 2023-4-18
J Mol Cell Cardiol. 2009-8-7
Arterioscler Thromb Vasc Biol. 2009-10
J Thromb Haemost. 2009-7
Arterioscler Thromb Vasc Biol. 2009-10
J Leukoc Biol. 2009-10
Zotero 插件