Differential regulation of human monocyte programmed cell death (apoptosis) by chemotactic factors and pro-inflammatory cytokines.
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.
Mangan
D F
DF
Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Wahl
S M
SM
D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D002630:Chemotactic Factors / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D004249:DNA Damage; D006801:Humans; D007158:Immunologic Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology*; D013997:Time Factors
D002630:Chemotactic Factors; D016207:Cytokines; D007375:Interleukin-1