The action of tumor necrosis factor-alpha on rat mast cells

Taking into account that cytokine tumor necrosis factor-alpha (TNF-alpha) a nd mast cells (MC) both are involved in inflammation, it seems of great imp ortance to recognize their relationships. Therefore, we have studied whethe r recombinant human TNF-alpha (rHuTNF-alpha) can cause histamine secretion from rat peritoneal MC. We have also examined the effect of this cytokine o n MC reactivity. We have established that TNF-alpha stimulates rat MC to hi stamine release in a concentration-dependent manner. TNF-alpha-induced hist amine secretion was evoked by concentrations > 10(-16) M and reached the ma ximum rate at a concentration of 10(-10) M (histamine release 17.1% +/- 1.9 %, mean +/- SEM), We have also noticed that pretreatment of MC with TNF-alp ha (in a concentration of 10(-16) M) significantly inhibited concanavalin A (ConA)-stimulated release of histamine, with the percent release decreasin g to 51% of the control value. Treatment of mast cells with TNF-alpha resul ted in a decrease of compound 48/80-dependent histamine release as well (th e percent released histamine fell to 85% of the control value). This altere d MC responsiveness was reversible. After 120 min of resting time, the MC r eactivity came back to the initial values. We have concluded that TNF-alpha appears to be a direct stimulus for MC to release histamine, and it may re gulate MC secretory function.