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 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.
Berkova
N
N
Laboratoire d'endocrinologie de la reproduction and Unité de recherche en genétique humaine et moléculaire, Centre de recherche de St-Françoise d'Assise, Québec, Canada.
Gilbert
C
C
Goupil
S
S
Yan
J
J
Korobko
V
V
Naccache
P H
PH
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D006242:Haptoglobins / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D009154:Mutation; D009504:Neutrophils / Q000187:drug effects*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015703:Antigens, CD; D006242:Haptoglobins; D006873:Hydroquinones; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; C048212:erbstatin