The influence of human endotoxemia on CD95-induced apoptosis.

Publication/Presentation Date

12-1-1998

Abstract

BACKGROUND: The responses of monocyte and neutrophil tumor necrosis factor receptor type 1 (TNFR-1) and TNFR-2 during systemic inflammation have been described previously. Several other members of the TNFR superfamily also appear to have regulatory roles in immunocyte function, including apoptosis. However, the response of these other receptor members, such as CD95, to systemic inflammation is unclear.

OBJECTIVES: To compare the response of CD95 with that of TNFR during systemic inflammation and to assess the influence of the inflammatory milieu on CD95 function.

SETTING: Adult clinical research center of a university hospital.

SUBJECTS AND METHODS: Five healthy male subjects were administered intravenous endotoxin (2 ng/kg), and systemic response was measured by cytokine analysis and receptor expression assays during a 48-hour period. CD95 function during systemic inflammation was assessed using a Jurkat cell bioassay for degree of apoptosis.

RESULTS: Monocyte and neutrophil CD95 expression exhibited changes parallel to that of TNFR following endotoxin injection. In contrast to soluble TNFR, which was transiently elevated during endotoxemia, soluble CD95 levels remained unchanged from baseline. Jurkat cells incubated in normal and post-endotoxin serum samples equally exhibited less than 10% spontaneous apoptosis. No soluble CD95 ligand was detectable in experimental human endotoxemia.

CONCLUSIONS: Cell-associated CD95 exhibited changes parallel to its receptor family member TNFR following endotoxin administration. Soluble CD95 is present in human serum samples, but the levels remained unchanged following endotoxin administration. No soluble CD95 ligand activity was detectable by enzyme-linked immunosorbent assay or by functional assay. The potential protective role of soluble CD95 in human serum samples against CD95 ligand-induced apoptosis remains to be defined.

Volume

133

Issue

12

First Page

1322

Last Page

1327

ISSN

0004-0010

Disciplines

Diagnosis | Medicine and Health Sciences | Other Analytical, Diagnostic and Therapeutic Techniques and Equipment | Radiology

PubMedID

9865650

Department(s)

Department of Radiology and Diagnostic Medical Imaging

Document Type

Article

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