Tazzyman Simon, Murdoch Craig, Yeomans James, Harrison Jack, Muthana Munitta
Department of Oncology.
School of Clinical Dentistry.
Hypoxia (Auckl). 2014 Nov 15;2:185-196. doi: 10.2147/HP.S49717. eCollection 2014.
Hypoxia plays a critical role in the pathobiology of various inflamed, diseased tissues, including malignant tumors, atherosclerotic plaques, myocardial infarcts, the synovia of rheumatoid arthritic joints, healing wounds, and sites of bacterial infection. These areas of hypoxia form when the blood supply is occluded and/or the oxygen supply is unable to keep pace with cell growth and/or infiltration of inflammatory cells. Macrophages are ubiquitous in all tissues of the body and exhibit great plasticity, allowing them to perform divergent functions, including, among others, patrolling tissue, combating invading pathogens and tumor cells, orchestrating wound healing, and restoring homeostasis after an inflammatory response. The number of tissue macrophages increases markedly with the onset and progression of many pathological states, with many macrophages accumulating in avascular and necrotic areas, where they are exposed to hypoxia. Recent studies show that these highly versatile cells then respond rapidly to the hypoxia present by altering their expression of a wide array of genes. Here we review the evidence for hypoxia-driven macrophage inflammatory responses in various disease states, and how this influences disease progression and treatment.
缺氧在各种炎症性病变组织的病理生物学过程中起着关键作用，这些组织包括恶性肿瘤、动脉粥样硬化斑块、心肌梗死、类风湿性关节炎关节的滑膜、愈合中的伤口以及细菌感染部位。当血液供应受阻和/或氧气供应无法跟上细胞生长和/或炎症细胞浸润时，就会形成这些缺氧区域。巨噬细胞在人体所有组织中普遍存在，并具有很强的可塑性，使其能够执行多种不同功能，包括组织巡逻、对抗入侵病原体和肿瘤细胞、协调伤口愈合以及在炎症反应后恢复体内平衡。随着许多病理状态的发生和进展，组织巨噬细胞数量显著增加，许多巨噬细胞积聚在无血管和坏死区域，在那里它们会暴露于缺氧环境。最近的研究表明，这些高度多功能的细胞随后会通过改变其多种基因的表达来快速响应存在的缺氧情况。在此，我们综述了缺氧驱动巨噬细胞在各种疾病状态下发生炎症反应的证据，以及这如何影响疾病进展和治疗。
