Ionophore A23187 releases histamine from normal mast cells apparently by promoting Ca influx (Foreman et al.). 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 accompanied by significant cytotoxicity but again Ca is required. In parallel studies, cultured RBL 1 cells were examined. These cells have apparently normal surface receptors for IgE, contain 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 non cytotoxic 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++, is temperature dependent but is uninhibitable by metabolic poisons (2 deoxyglucose, dinitrophenol, CN-). Taken together these studies suggest that the RBL 1 cells may fail to release histamine normally because of a block in the stage(s) after Ca++ influx. They underline the importance of ruling out cytotoxicity in inophore induced phenomena.
|State||Published - Jan 1 1975|