TNF-Induced Haptoglobin Release from Human Neutrophils: Pivotal Role of the TNF p55 Receptor

Haptoglobin (Hp), TNF-alpha, and neutrophils are parts of a highly interactive ensemble participating in inflammatory processes. Hp is taken up by neutrophils, stored within a cytoplasmic granular compartment, and is secreted during phagocytosis by those cells. In the present study, the effects of T...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1999-05, Vol.162 (10), p.6226-6232
Main Authors: Berkova, Nadia, Gilbert, Caroline, Goupil, Serge, Yan, Ju, Korobko, Vyatcheslav, Naccache, Paul H
Format: Article
Language:English
Subjects:
Antigens, CD - genetics
Antigens, CD - metabolism
Dose-Response Relationship, Drug
Fluorescent Antibody Technique
Haptoglobins - isolation & purification
Haptoglobins - secretion
Humans
Hydroquinones - pharmacology
Mutation
Neutrophils - drug effects
Phosphorylation
Protein-Tyrosine Kinases - antagonists & inhibitors
Protein-Tyrosine Kinases - metabolism
Receptors, Tumor Necrosis Factor - genetics
Receptors, Tumor Necrosis Factor - metabolism
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Tumor Necrosis Factor-alpha - pharmacology
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Summary:Haptoglobin (Hp), TNF-alpha, and neutrophils are parts of a highly interactive ensemble participating in inflammatory processes. Hp is taken up by neutrophils, stored within a cytoplasmic granular compartment, and is secreted during phagocytosis by those cells. In the present study, the effects of TNF-alpha on the release of Hp from human neutrophils were investigated. Incubation of neutrophils with TNF-alpha induced the release of Hp from cells in a time- and concentration-dependent manner as revealed by Western blot analysis and immunofluorescence. The release of Hp induced by TNF-alpha was not due to nonspecific lysis of the cells. TNF-alpha is a highly pleiotropic cytokine that mediates its effects by binding to two distinct receptors (p55 and p75). Administration of TNF-alpha mutants binding specifically either to the p55 or to the p75 TNF receptors showed that there is a preference of TNF-alpha for the p55 receptor in the mediation of Hp release by neutrophils. A stimulated release of Hp was also induced by the chemotactic tripeptide fMLP. The TNF-alpha-induced release of Hp from neutrophils was inhibited by erbstatin, a tyrosine kinase inhibitor. These findings suggest that TNF-alpha may promptly increase the level of Hp at sites of infection or injury, leading to the modulation of the acute inflammatory response.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.162.10.6226