Ionophore A 23187 induced histamine release from rat mast cells and rat basophil leukemia (RBL 1) cells

Ionophore A 23187 releases histamine from normal mast cells apparently by promoting Ca⁺⁺ influx (Foreman et al, Nature 245: 249, 1973). In the authors hands at concentrations of >0.2 μg/ml release occurs in 1 to 2 min, is blocked by metabolic inhibitors, and is unaccompanied by cytotoxicity (trypan blue uptake, lactic dehydrogenase (LDH) release). At higher doses (0.5 μg/ml) histamine release is followed by significant cytotoxicity, but again Ca⁺⁺ is required. In parallel studies, the authors examined cultured rat basophilic leukemia (RBL 1) cells. These cells, which apparently have normal surface receptors for IgE, contained approx. 700 ng histamine/10⁶ cells but did not release histamine when IgE mediated release was looked for. They do not respond to doses of ionophore which would be expected to give noncytotoxic histamine release. At higher doses histamine release is preceded by progressive LDH release: LDH release is 75% complete at 5 min whereas 10 min are required for 75% maximal histamine release. This reaction requires Ca⁺⁺ and is temperature dependent but is not inhibited by metabolic poisons (2 deoxyglucose, dinitrophenol, CN^-). These studies suggest that either Ca⁺⁺ does not enter into these cells normally or that one or more mechanisms which are ordinarily triggered by the changes in Ca⁺⁺ flow are unresponsive in the RBL 1 cells. These studies also underline the importance of ruling out cytotoxicity in ionophore induced phenomena.