Ravi Saranya, Mitchell Tanecia, Kramer Philip, Chacko Balu, Darley-Usmar Victor M
Department of Pathology, UAB Mitochondrial Medicine Laboratory, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Int J Biochem Cell Biol. 2014 Aug;53:202-207. doi: 10.1016/j.biocel.2014.05.019. Epub 2014 May 23.
The mitochondrion plays a crucial role in the immune system particularly in regulating the responses of monocytes and macrophages to tissue injury, pathogens, and inflammation. In systemic diseases such as atherosclerosis and chronic kidney disease (CKD), it has been established that disruption of monocyte and macrophage function can lead to chronic inflammation. Polarization of macrophages into the pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes results in distinct metabolic reprograming which corresponds to the progression and resolution of inflammation. In this review, we will discuss the role of the mitochondrion in monocyte and macrophage function and how these cells specifically influence the pathophysiology of atherosclerosis and CKD. We propose that assessing monocyte bioenergetics in different disease states could (1) enhance our understanding of the energetic perturbations occurring in systemic inflammatory conditions and (2) aid in identifying therapeutic interventions to mitigate these disorders in patients.
线粒体在免疫系统中发挥着关键作用,特别是在调节单核细胞和巨噬细胞对组织损伤、病原体及炎症的反应方面。在动脉粥样硬化和慢性肾脏病(CKD)等全身性疾病中,单核细胞和巨噬细胞功能的破坏会导致慢性炎症,这一点已得到证实。巨噬细胞向促炎(M1)和抗炎(M2)表型的极化会导致明显的代谢重编程,这与炎症的进展和消退相对应。在本综述中,我们将讨论线粒体在单核细胞和巨噬细胞功能中的作用,以及这些细胞如何具体影响动脉粥样硬化和CKD的病理生理学。我们认为,评估不同疾病状态下单核细胞的生物能量学可以(1)增进我们对全身性炎症状态下发生的能量紊乱的理解,(2)有助于确定减轻患者这些疾病的治疗干预措施。