title: Lipopolysaccharide, tumor necrosis factor-alpha, and IL-1 beta prevent programmed cell death (apoptosis) in human peripheral blood monocytes.
abstract: Human peripheral blood monocytes progressively lose viability when cultured in the absence of serum, cytokines, or other stimuli. In this study, we investigated whether monocyte death results from membrane damage (i.e., necrosis) or internally regulated processes [i.e., programmed cell death (PCD) or apoptosis]. Our results clearly indicated that monocytes die by PCD when cultured without stimulation. Death was associated with fragmentation of DNA into integer multiples of approximately 200 bp, a decrease in cell size, condensation of the nucleus and cytoplasmic organelles, and membrane blebbing, all of which are cardinal features of PCD. Monocytes exposed to nonphysiologic conditions such as acidic media (pH 4.2), 56 degrees C for 30 min, or freezing and thawing were killed without concomitant DNA fragmentation, indicating that DNA fragmentation was not a result of cell death per se. Addition of Escherichia coli LPS, a potent monocyte activating agent, in concentrations as low as 0.1 ng/ml caused a marked increase in monocyte survival and prevented DNA fragmentation. Moreover, exogenous human rTNF-alpha or IL-1 beta also prevented PCD, suggesting that PCD is regulated by certain cytokines released from LPS-stimulated monocytes. The results indicate that in the absence of appropriate stimulation, monocytes are programmed to undergo a sequence of molecular events leading to cell death. Regulation of PCD may be an important homeostatic mechanism for controlling the number of monocytes available to respond to infection, wound healing, and tumor growth.
authors.affiliation: Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
authors.forename: D F
authors.initials: DF
authors.lastname: Mangan
authors.forename: G R
authors.initials: GR
authors.lastname: Welch
authors.forename: S M
authors.initials: SM
authors.lastname: Wahl
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004247:DNA / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D003470:Culture Media; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D004247:DNA