Department of Biological Sciences, GDC College, Vikram University, Ujjain, India.
J Innate Immun. 2010;2(3):204-15. doi: 10.1159/000296507. Epub 2010 Mar 16.
Monocytes and macrophages are central cells of the innate immune system, responsible for defending against diverse pathogens. While they originate from a common myeloid precursor and share functions in innate immunity, each has a very distinct life span finely tuned by the apoptotic caspases. Normally, circulating monocytes are short-lived and undergo spontaneous apoptosis on a daily basis. Macrophages, however, have a longer life span. In chronic inflammatory diseases and, as recently recognized, in the tumor microenvironment, the inhibition of the apoptotic program promotes monocyte survival contributing to the accumulation of macrophages and the persistence of an inflammatory milieu. A complex network of differentiation factors and inflammatory stimuli determine monocyte/macrophage life span by blocking the apoptotic pathway and activating a myriad of survival pathways. Our understanding of apoptosis has flourished over the last decade, and its relevance in the regulation of the immune system is now indisputable. Nevertheless, how the complicated networks of survival and apoptotic regulators are integrated to determine cellular life span remains elusive. This review summarizes the contribution of the caspases and their regulators in monocyte/macrophage cell fate and discusses how these molecules orchestrate the initiation, maintenance, and resolution of inflammation. More provocatively, we discuss possible strategies to control inflammation by manipulating leukocyte life span.
单核细胞和巨噬细胞是先天免疫系统的核心细胞，负责抵御各种病原体。虽然它们起源于共同的髓样前体，并在先天免疫中具有共同的功能，但每个细胞的寿命都非常独特，凋亡半胱天冬酶精细地调节着它们的寿命。正常情况下，循环中的单核细胞寿命较短，每天都会自发凋亡。然而，巨噬细胞的寿命较长。在慢性炎症性疾病中，以及最近在肿瘤微环境中被认识到的，凋亡程序的抑制促进单核细胞的存活，导致巨噬细胞的积累和炎症环境的持续存在。分化因子和炎症刺激的复杂网络通过阻断凋亡途径并激活无数的存活途径来决定单核细胞/巨噬细胞的寿命。我们对细胞凋亡的理解在过去十年中得到了蓬勃发展，其在免疫系统调节中的重要性现在已不容置疑。然而，存活和凋亡调节因子的复杂网络如何整合来决定细胞寿命仍然难以捉摸。这篇综述总结了半胱天冬酶及其调节因子在单核细胞/巨噬细胞细胞命运中的作用，并讨论了这些分子如何协调炎症的启动、维持和消退。更具挑战性的是，我们讨论了通过操纵白细胞寿命来控制炎症的可能策略。
