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Published on: April 9, 2013
The functional role of 55- and 75-kDa tumour necrosis factor receptors in human polymorphonuclear cells in vitro
Abstract:
The expression and biological role of 55- and 75-kDa tumour necrosis factor-receptors (TNF-RI and TNF-RII) in human polymorphonuclear cells (PMN) in vitro were studied using agonistic rabbit polyclonal anti-TNF-R antibodies. PMN express TNF-RII predominantly, and release the superoxide anion on stimulation by human recombinant lymphotoxin (LT) in vitro. Anti-TNF-RI but not anti-TNF-RII antibody stimulated the superoxide release mimicking LT. Release of the elastase from azurophilic granule of PMN was augmented by LT in vitro. Anti-TNF-RI but not anti-TNF-RII antibody augmented the elastase release. Release of the lactoferrin from the specific granules of PMN was enhanced by LT in vitro. Anti-TNF-RI but not anti-TNF-RII antibody augmented the elastase release. Release of the lactoferrin from the specific granules of PMN was enhanced by LT in vitro. Anti-TNF-RI but not anti-TNF-RII antibody enhanced the lactoferrin release. These antibodies failed to co-stimulate these PMN functions. The adhesiveness of PMN to a plastic plate and the expression of Mac-1 on PMN were upregulated by LT in vitro. Anti-TNF-RI but not anti-TNF-RII antibody upregulated the adhesiveness and Mac-1 expression of PMN mimicking LT. Though anti-TNF-RII antibody by itself did not alter the adhesiveness and marginally suppressed Mac-1 expression, it maintained the adhesiveness and adhesion molecule expression in the presence of anti-TNF-RI antibody. In summary, PMN predominantly express TNF-RII, the signalling of LT (and TNF) in PMN is mediated mainly by TNF-RI, and the adhesion function can be modulated also by TNF-RII when TNF-RI is stimulated.
Insights
Human polymorphonuclear cells (PMN) primarily express tumour necrosis factor-receptor II (TNF-RII), but signalling of lymphotoxin (LT) and TNF primarily occurs via TNF-RI. This study investigates their distinct roles in PMN function.
Area of Science:
- Immunology
- Cell Biology
Background:
- Tumour necrosis factor-receptors (TNF-R) mediate crucial cellular responses.
- Polymorphonuclear cells (PMN) play a key role in inflammatory processes.
- Understanding TNF-R function in PMN is vital for inflammatory disease research.
Purpose of the Study:
- To elucidate the distinct roles of TNF-RI and TNF-RII in human PMN.
- To investigate the signaling pathways of lymphotoxin (LT) and TNF in PMN.
- To determine the impact of TNF-R activation on PMN functions like superoxide release, granule exocytosis, and adhesion.
Main Methods:
- Utilized agonistic rabbit polyclonal anti-TNF-R antibodies to stimulate TNF-RI and TNF-RII.
- Studied human PMN in vitro.
- Assessed superoxide anion release, elastase and lactoferrin release, and Mac-1 expression.
Main Results:
- PMN predominantly express TNF-RII, but LT/TNF signaling is mainly mediated by TNF-RI.
- Anti-TNF-RI antibody stimulated superoxide release, elastase, and lactoferrin release, mimicking LT.
- Anti-TNF-RI antibody upregulated PMN adhesiveness and Mac-1 expression; TNF-RII modulated adhesion when TNF-RI was stimulated.
Conclusions:
- Human PMN primarily express TNF-RII, but TNF-RI mediates key LT/TNF signaling.
- TNF-RI is the primary mediator of LT-induced superoxide release, granule exocytosis, and adhesion molecule upregulation in PMN.
- TNF-RII plays a modulatory role in PMN adhesion, particularly in conjunction with TNF-RI activation.
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