Vlahos Ross, Bozinovski Steven
Department of Pharmacology and Therapeutics, Lung Health Research Centre, The University of Melbourne , Parkville, VIC , Australia.
Front Immunol. 2014 Sep 10;5:435. doi: 10.3389/fimmu.2014.00435. eCollection 2014.
Alveolar macrophages (AMs) represent a unique leukocyte population that responds to airborne irritants and microbes. This distinct microenvironment coordinates the maturation of long-lived AMs, which originate from fetal blood monocytes and self-renew through mechanisms dependent on GM-CSF and CSF-1 signaling. Peripheral blood monocytes can also replenish lung macrophages; however, this appears to occur in a stimuli specific manner. In addition to mounting an appropriate immune response during infection and injury, AMs actively coordinate the resolution of inflammation through efferocytosis of apoptotic cells. Any perturbation of this process can lead to deleterious responses. In chronic obstructive pulmonary disease (COPD), there is an accumulation of airway macrophages that do not conform to the classic M1/M2 dichotomy. There is also a skewed transcriptome profile that favors expression of wound-healing M2 markers, which is reflective of a deficiency to resolve inflammation. Endogenous mediators that can promote an imbalance in inhibitory M1 vs. healing M2 macrophages are discussed, as they are the plausible mechanisms underlying why AMs fail to effectively resolve inflammation and restore normal lung homeostasis in COPD.
肺泡巨噬细胞（AMs）是一种独特的白细胞群体，可对空气传播的刺激物和微生物作出反应。这种独特的微环境协调长寿AMs的成熟，AMs起源于胎儿血液单核细胞，并通过依赖GM-CSF和CSF-1信号传导的机制进行自我更新。外周血单核细胞也可以补充肺巨噬细胞；然而，这似乎是以刺激特异性的方式发生的。除了在感染和损伤期间引发适当的免疫反应外，AMs还通过凋亡细胞的胞葬作用积极协调炎症的消退。该过程的任何扰动都可能导致有害反应。在慢性阻塞性肺疾病（COPD）中，存在不符合经典M1/M2二分法的气道巨噬细胞积聚。还存在偏向于伤口愈合M2标志物表达的转录组谱，这反映了炎症消退的缺陷。本文讨论了可促进抑制性M1与愈合性M2巨噬细胞失衡的内源性介质，因为它们是AMs在COPD中未能有效解决炎症并恢复正常肺稳态的潜在机制。
