Differential regulation of human monocyte programmed cell death (apoptosis) by chemotactic factors and pro-inflammatory cytokines.
Differential regulation of human monocyte programmed cell death (apoptosis) by chemotactic factors and pro-inflammatory cytokines.
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DOI：
10.4049/jimmunol.147.10.3408
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发表时间：
1991-11
影响因子：
4.4
通讯作者：
D. Mangan;S. Wahl
中科院分区：
文献类型：
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作者：
D. Mangan;S. Wahl
在缺乏适当刺激的情况下，单核细胞发生程序性细胞死亡（PCD）或凋亡。IL-1 β和tnf - α可阻止单核细胞PCD，这表明炎症过程中释放的生物活性肽可能调节单核细胞的生存能力。为了探索这种可能性，我们评估了几种趋化因子和促炎细胞因子调节PCD的能力。募集因子，FMLP， C片段C5a，单核细胞趋化蛋白-1，或转化生长因子-1，不能从PCD中拯救单核细胞，也不能增强PCD，而除了IL-1 β和tnf - α之外的几种炎症细胞因子，包括粒细胞-单核细胞csf和ifn - γ，可以阻止单核细胞PCD，前提是这些细胞因子在培养物中持续保持足够水平。细胞因子介导的PCD抑制可被特异性抗血清阻断，排除了LPS污染引起的潜在影响。当在相同浓度下测试时，IL-2、IL-4和IL-6对PCD没有影响，这表明细胞因子对单核细胞PCD的调节具有选择性。由于单核细胞在激活时产生IL-1 β， tnf - α和粒细胞单核细胞CSF，数据表明自分泌和旁分泌控制细胞存活和积累。研究结果还表明，募集到炎症部位的单核细胞在缺乏特定细胞因子和/或其他阻止这一过程的刺激的情况下会经历PCD。
In the absence of appropriate stimuli, monocytes undergo programmed cell death (PCD) or apoptosis. IL-1 beta and TNF-alpha prevent monocyte PCD, which suggests that viability may be regulated by biologically active peptides released during inflammation. To explore this possibility, we evaluated several chemotactic factors and pro-inflammatory cytokines for their ability to regulate PCD. The recruitment factors, FMLP, C fragment C5a, monocyte chemotactic protein-1, or transforming growth factor-beta 1, were incapable of rescuing monocytes from PCD nor did they enhance PCD, whereas several inflammatory cytokines in addition to IL-1 beta and TNF-alpha, including granulocyte-monocyte-CSF and IFN-gamma, prevented monocyte PCD provided that sufficient levels of these cytokines were continuously maintained in the cultures. Cytokine-mediated inhibition of PCD could be blocked by specific antisera, ruling out potential effects caused by LPS contamination. When tested at equivalent concentrations, IL-2, IL-4, and IL-6 had no effect on PCD indicating selectivity in cytokine modulation of monocyte PCD. Because monocytes produce IL-1 beta, TNF-alpha, and granulocyte-monocyte CSF when activated, the data suggest autocrine as well as paracrine control of cell survival and accumulation. The results also suggest that monocytes recruited to a site of inflammation will undergo PCD in the absence of specific cytokines and/or other stimuli that block this process.