Mangan D F, Mergenhagen S E, Wahl S M
Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, MD.
J Periodontol. 1993 May;64(5 Suppl):461-6.
Apoptosis or programmed cell death is a physiological form of cell suicide that is profoundly influenced by the extracellular microenvironment. Apoptosis is characterized by a cascade of genetic and biochemical events that cause cell shrinkage, condensation of cytoplasmic and nuclear material, cleavage of chromosomal DNA into oligonucleosomesized (approximately 200 bp) fragments, and enhanced recognition of the dying cell by phagocytes. Apoptosis differs fundamentally from necrosis, the pathological form of cell death, in which the cell swells and lyses. The capacity to selectively induce apoptosis in leukocytes might be an important physiological mechanism for controlling accumulation of these cells in inflammatory lesions. In this paper, we review our data on apoptosis in human monocytes, cells which contribute both to the persistence and resolution of chronic inflammation. Apoptosis can be initiated when monocytes are cultured in the absence of appropriate exogenous stimulation. For example, addition of chemotactic factors is insufficient to block apoptosis. However, apoptosis in monocytes can be inhibited by adherence in the presence of serum, by microbial products such as lipopolysaccharide, or by certain pro-inflammatory cytokines, such as interleukin 1 and tumor necrosis factor-alpha. Cytokines derived from type 1 helper T cells (e.g., interferon-gamma) inhibit apoptosis whereas those derived from type 2 helper T cells (e.g., interleukin-4) enhance apoptosis in activated monocytes. Thus, cytokines derived from monocytes as well as T cells modulate apoptosis, implicating both autocrine and paracrine regulatory circuits in monocyte survival. The capacity to therapeutically regulate monocyte apoptosis promises to have tremendous value in promoting rapid healing or reducing the immunopathogenesis of chronic inflammation.
凋亡或程序性细胞死亡是一种细胞自杀的生理形式，受到细胞外微环境的深刻影响。凋亡的特征是一系列遗传和生化事件，这些事件导致细胞萎缩、细胞质和核物质浓缩、染色体DNA裂解成寡核小体大小（约200bp）的片段，以及吞噬细胞对垂死细胞的识别增强。凋亡与坏死（细胞死亡的病理形式）有根本区别，坏死时细胞肿胀并裂解。在白细胞中选择性诱导凋亡的能力可能是控制这些细胞在炎症病变中积聚的重要生理机制。在本文中，我们回顾了我们关于人类单核细胞凋亡的数据，这些细胞对慢性炎症的持续和消退都有作用。当单核细胞在没有适当外源性刺激的情况下培养时，凋亡可以启动。例如，添加趋化因子不足以阻止凋亡。然而，单核细胞中的凋亡可以通过在血清存在下的黏附、微生物产物如脂多糖或某些促炎细胞因子如白细胞介素1和肿瘤坏死因子-α来抑制。来自1型辅助性T细胞的细胞因子（如干扰素-γ）抑制凋亡，而来自2型辅助性T细胞的细胞因子（如白细胞介素-4）增强活化单核细胞中的凋亡。因此，来自单核细胞以及T细胞的细胞因子调节凋亡，这意味着自分泌和旁分泌调节回路都参与单核细胞的存活。治疗性调节单核细胞凋亡的能力有望在促进快速愈合或减少慢性炎症的免疫发病机制方面具有巨大价值。
