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Role of mast cells and monoamines in the thrombocytopaenia and mortality elicited by tumour necrosis factor in mice

Published in Immunology. 1998, vol. 95, no. 1, p. 111-6
Abstract We explored the thrombocytopaenia elicited by the i.v. injection of mouse recombinant tumour necrosis factor (TNF) in mice. Injection of 10 micrograms of TNF led to a thrombocytopaenia (evident after 0.5 hr) which was caused by decreased platelet survival, as seen by the injection of labelled platelets. TNF-induced thrombocytopaenia was not prevented by heparin, nor by depletion of either fibrinogen or C'. TNF-induced thrombocytopaenia was markedly attenuated in mice treated with reserpine, an agent that depletes monoamines from mast cells and other cells, and in the mast-cell-deficient WWv mice. In vitro, TNF elicited a modest release of monoamine from peritoneal mast cells and from a mast cell line. When mice are injected with 3H-serotonin (3H-5HT) before TNF, TNF injection increased the plasma 3H-5HT content 1 hr later, modifications absent in reserpine pretreated or mast-cell-deficient mice. 3H-5HT content of the small intestine was markedly depleted in TNF-injected mice, suggesting that this organ is the source of the plasma 3H-5HT. Drop in body temperature and mortality induced by TNF were also attenuated in mast-cell-deficient, and in reserpine pretreated mice. These results indicate that TNF can induce a release of monoamines from mast cells, mainly from those of the small intestine, a process that contributes to TNF-induced thrombocytopaenia and mortality.
Keywords Adrenergic Uptake Inhibitors/therapeutic useAnimalsBody Temperature/drug effectsCell LineCells, CulturedInjections, IntravenousIntestine, Small/metabolismMast Cells/drug effects/metabolismMiceMice, Inbred C57BLMice, Inbred CBAMice, Mutant StrainsPlatelet Count/drug effectsRecombinant Proteins/pharmacologyReserpine/therapeutic useSerotonin/metabolismThrombocytopenia/immunology/metabolism/mortalityTritium/diagnostic useTumor Necrosis Factor-alpha/pharmacology
PMID: 9767465
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Research group Facteurs influençants le développement pulmonaire: étude translationnelle chez l'animal et l'homme (182)
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PIGUET, Pierre et al. Role of mast cells and monoamines in the thrombocytopaenia and mortality elicited by tumour necrosis factor in mice. In: Immunology, 1998, vol. 95, n° 1, p. 111-6. doi: 10.1046/j.1365-2567.1998.00536.x https://archive-ouverte.unige.ch/unige:74300

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