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Concanavalin A (Con A) and phytohemagglutinin (PHA) released histamine from hamster mast cells incubated in a serum-free medium. Concentrations of Con A and PHA approximating those optimal for transforming lymphocytes also released maximal amounts of histamine without apparent cytotoxicity. Higher concentrations of mitogen inhibited both lymphocyte transformation and histamine release. Incubation at 37 C for 15 min released histamine, although longer times were more effective. Supernatants from cultured hamster splenocytes stimulated with Con A also released histamine from added mast cells. However, the effect could be inhibited by the addition of 0.1 M methyl alpha-D-mannoside or by passing the spleen cell culture supernatants through Sephadex G-75 to remove Con A. This mitogen-induced release of mast cell histamine is therefore not mediated by a lymphokine but probably results from a direct interaction of mitogens with receptors on mast cells.
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