Publication
Title
Regulation of neutrophil apoptosis by tumor necrosis factor-: requirement for TNFR55 and TNFR75 for induction of apoptosis in vitro
Author
Abstract
Granulocyte apoptosis is an important mechanism underlying the removal of redundant neutrophils from an inflammatory focus. The ability of many proinflammatory agents to impede this event suggests that such agents act not only in a priming or secretagogue capacity but also increase neutrophil longevity by delaying apoptosis. We have examined whether this hypothesis holds true for all neutrophil priming agents, in particular tumor necrosis factor- (TNF-), which has been variably reported to either induce, delay, or have no effect on neutrophil apoptosis. After 20 hours coincubation TNF- inhibited neutrophil apoptosis; however, more detailed analysis demonstrated its ability to promote apoptosis in a subpopulation of cells at earlier (2 to 8 hours) times. Formyl-Met-Leu-Phe, platelet-activating factor, inositol hexakisphosphate, lipopolysaccharide, leukotriene B4 , and granulocyte-macrophage colony-stimulating factor all inhibited apoptosis at 6 and 20 hours. The early proapoptotic effect of TNF- was concentration-dependent (EC50 2.8 ng/mL), abolished by TNF- neutralizing antibody, and was not associated with any change in cell viability or recovery. Of relevance to the inflamed site, the ability of TNF- to accelerate apoptosis was lost if neutrophils were primed with 1 µmol/L PAF or aged for 6 hours before TNF- addition. The TNFR55-selective TNF- mutants (E146K, R32W-S86T) induced neutrophil apoptosis but with a potency 14-fold lower than wild-type TNF-. Although the TNFR75-selective mutant (D143F ) did not induce apoptosis, blocking antibodies to both receptor subtypes abolished TNF--stimulated apoptosis. Hence, TNF- has the unique ability to induce apoptosis in human neutrophils via a mechanism where TNFR75 facilitates the dominant TNFR55 death effect. This may be an important mechanism controlling neutrophil longevity and clearance in vivo.
Language
English
Source (journal)
Blood / American Society of Hematology. - New York, N.Y.
Publication
New York, N.Y. : 1997
ISSN
0006-4971
Volume/pages
90:7(1997), p. 2772-2783
ISI
A1997XY70300031
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 10.06.2009
Last edited 20.10.2017
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