Anti-fas induces apoptosis and proliferation in human dermal fibroblasts: Differences between foreskin and adult fibroblasts

Apoptosis, or programmed cell death, is a naturally occurring process mediated by extracellular signals. We studied anti‐Fas (CD95/Apo‐1) antibody‐induced apoptosis in cultured human foreskin and adult dermal fibroblasts. Induction of apoptosis was identified by fluorescence in situ DNA end‐labeling...

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Bibliographic Details
Published in:Journal of cellular physiology 1998-04, Vol.175 (1), p.19-29
Main Authors: Jelaska, Ante, Korn, Joseph H.
Format: Article
Language:English
Subjects:
Adult
Age Factors
Antibodies, Blocking
Antibody Specificity
Apoptosis - drug effects
Apoptosis - physiology
Cell Differentiation - physiology
Cell Division - physiology
Ceramides - pharmacology
Clone Cells
Fas Ligand Protein
Fibroblasts - chemistry
Fibroblasts - cytology
Humans
Infant, Newborn
Membrane Glycoproteins - immunology
Membrane Glycoproteins - metabolism
Skin - cytology
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Summary:Apoptosis, or programmed cell death, is a naturally occurring process mediated by extracellular signals. We studied anti‐Fas (CD95/Apo‐1) antibody‐induced apoptosis in cultured human foreskin and adult dermal fibroblasts. Induction of apoptosis was identified by fluorescence in situ DNA end‐labeling. Anti‐Fas antibody induced apoptosis in fibroblasts in a dose‐ and time‐dependent manner. Adult dermal skin fibroblasts were more susceptible to anti‐Fas antibody‐induced apoptosis than foreskin fibroblasts, with 21–52% dead cells in different strains. In foreskin fibroblasts, anti‐Fas antibody (1.0 μg/ml) predominantly induced proliferation ([3H]thymidine incorporation increased to 115–165% of control level) and only low levels of apoptotic cell death after 48 hours of treatment. No induction of proliferation by anti‐Fas was found in the adult fibroblasts. Addition of tumor necrosis factor‐α (TNF‐α) slightly augmented the anti‐Fas antibody‐induced apoptosis in both cell types. When we examined the levels of Fas expression using flow cytometry, we found two‐ to threefold higher Fas expression in adult fibroblasts. C6‐ceramide treatment, which induces Fas‐independent apoptosis, gave similar levels of cell death in both foreskin and adult fibroblasts. No proliferation was observed in C6‐ceramide‐treated fibroblasts. Thus, this difference in apoptosis between adult dermal and foreskin fibroblasts appears to be related to the level of Fas expression. When clones of foreskin fibroblasts were examined, there was heterogeneity of anti‐Fas antibody‐induced apoptosis and proliferation in the cloned fibroblast subpopulations, but this was not correlated with differences in Fas expression. Alterations in fibroblast populations during the process of differentiation and aging may result from selective loss of apoptosis‐susceptible populations. J. Cell. Physiol. 175:19–29, 1998. © 1998 Wiley‐Liss, Inc.
ISSN:0021-9541
1097-4652
DOI:10.1002/(SICI)1097-4652(199804)175:1<19::AID-JCP3>3.0.CO;2-F