Role of mast cells and monoamines in the thrombocytopaenia and mortality elicited by tumour necrosis factor in mice.
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.
Department of Pathology, University of Geneva, Geneva, Switzerland.
P F
PF
Piguet
C
C
Vesin
J
J
Guo
Y
Y
Donati
C
C
Barazzone
D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D007275:Injections, Intravenous; D007421:Intestine, Small / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012110:Reserpine / Q000627:therapeutic use; D012701:Serotonin / Q000378:metabolism*; D013921:Thrombocytopenia / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018759:Adrenergic Uptake Inhibitors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D012701:Serotonin; D012110:Reserpine