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STEM CELL FACTOR POTENTIATES HISTAMINE SECRETION BY MULTIPLE MECHANISMS, BUT DOES NOT AFFECT tumour necrosis factor‐α RELEASE FROM RAT MAST CELLS

The effect of stem cell factor (SCF) on histamine and tumour necrosis factor‐α (TNF‐α) release from rat peritoneal mast cells (PMC) was determined and the intracellular pathways involved in the potentiation of histamine secretion were investigated. The effects of SCF (2–100 ng/ml) were examined following both short‐term (0 and 20 min) and long‐term (up to 24 hr) preincubations with SCF. Pretreatment of PMC with SCF for 0 min (concurrent) or 20 min did not induce histamine secretion directly, but significantly increased antigen (Ag)‐induced histamine secretion. SCF potentiated Ag‐induced intracellular Ca2+ increase and calcium ionophore A23187‐induced histamine secretion. Pertussis toxin (PT) inhibited SCF‐induced potentiation of IgE‐dependent histamine secretion, indicating that PT‐sensitive G‐proteins are involved in the immediate effects of SCF. In long‐term incubation experiments, SCF pretreatment for 18–24 hr significantly enhanced Ag‐induced histamine secretion, but did not affect Ag‐induced intracellular Ca2+ levels. The effects of long‐term incubation with SCF, but not the short‐term effects, were blocked by cycloheximide. Interestingly, spontaneous and Ag‐induced TNF‐α release from rat PMC were not affected by pretreatment with SCF (2–500 ng/ml) for 1 to 24 hr. Thus, through immediate and delayed mechanisms, SCF potentiates histamine release from PMC, but has no effect on TNF‐α release. The regulation of MC by SCF may be important in allergic and other inflammatory diseases.