ROLE OF MAST-CELLS AND MONOAMINES IN THE THROMBOCYTOPAENIA AND MORTALITY ELICITED BY TUMOR-NECROSIS-FACTOR IN MICE

We explored the thrombocytopaenia elicited by the i.v. injection of mo use recombinant tumour necrosis factor (TNF) in mice. Injection of 10 mu g of TNF led to a thrombocytopaenia (evident after 0.5 hr) which wa s caused by decreased platelet survival, as seen by the injection of l abelled platelets. TNF-induced thrombocytopaenia was not prevented by heparin, nor by depletion of either fibrinogen or C'. TNF-induced thro mbocytopaenia 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 l ine. When mice are injected with H-3-serotonin (H-3-5HT) before TNF, T NF injection increased the plasma H-3-5HT content 1 hr later, modifica tions absent in reserpine pretreated or mast-cell-deficient mice. H-3- 5HT content of the small intestine was markedly depleted in TNF-inject ed mice, suggesting that this organ is the source of the plasma H-3-5H T. Drop in body temperature and mortality induced by TNF were also att enuated in mast-cell-deficient, and in reserpine pretreated mice. Thes e results indicate that TNF can induce a release of monoamines from ma st cells, mainly from those of the small intestine, a process that con tributes to TNF-induced thrombocytopaenia and mortality.