Functional expression of Fas and Fas ligand on human gut lamina propria T lymphocytes. A potential role for the acidic sphingomyelinase pathway in normal immunoregulation
Details
Serval ID
serval:BIB_9BFB78CA6D4D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Functional expression of Fas and Fas ligand on human gut lamina propria T lymphocytes. A potential role for the acidic sphingomyelinase pathway in normal immunoregulation
Journal
Journal of Clinical Investigation
ISSN
0021-9738 (Print)
Publication state
Published
Issued date
01/1996
Volume
97
Number
2
Pages
316-22
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan 15
Research Support, Non-U.S. Gov't --- Old month value: Jan 15
Abstract
The expression and function of Fas (CD95/APO-1), a cell surface receptor directly responsible for triggering cell death by apoptosis, was investigated on human T lymphocytes resident within the intestinal lamina propria, a major site of antigen challenge and persistent lymphocyte activation. Three color immunofluorescence and FACS analysis indicated that virtually all freshly isolated human gut lamina propria T lymphocytes (T-LPL) express Fas, together with the marker of progress activation CD45R0. A discrete fraction of freshly isolated T-LPL also constitutively expressed Fas ligand (FasL), perhaps as a result of recent in vivo activation. Importantly, whereas Fas cross-linking did not result in apoptosis induction in peripheral blood T lymphocytes (T-PBL), Fas was found to be fully effective in generating the apoptotic signal in T-LPL. This was associated with the activation of an acidic sphingomyelinase and with ceramide generation, early events known to be involved in Fas-mediated apoptotic signaling. By contrast, acidic sphingomyelinase activation and ceramide production were not detectable in T-PBL after Fas cross-linking. However C2-ceramide, a cell permeant synthetic analog of ceramide, could efficiently induce apoptosis in T-LPL and T-PBL when added exogenously. These data indicate that T-LPL constitutively express both Fas and FasL and that Fas cross-linking generates signals resulting in sphingomyelin hydrolysis and apoptosis, outlining a potential mechanism involved in intestinal tolerance. Moreover, they provide the first evidence of a role for ceramide-mediated pathways in normal immunoregulation.
Keywords
Antigens, CD45/metabolism
Antigens, CD95/*metabolism
Apoptosis
Ceramides/pharmacology
Fas Ligand Protein
Flow Cytometry
Humans
*Immunity, Mucosal
Intestinal Mucosa/cytology/*immunology
Membrane Glycoproteins/*metabolism
Sphingomyelin Phosphodiesterase/*physiology
Sphingomyelins/metabolism
T-Lymphocytes/*metabolism
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 16:18
Last modification date
20/08/2019 16:02