Supernatants from macrophages stimulated with microcystin-LR induce electrogenic intestinal response in rabbit ileum

Microcystin-LR is a cyclic heptapeptide hepatotoxin produced by the cyanoba cterium Microcystis aeruginosa. This microorganism often forms toxic blooms in freshwater lakes and reservoirs for drinking water supply, producing se rious disorders in humans and animals. Some have suggested that certain bio logical activities of microcystin may depend upon the stimulation of immune cells. Therefore, the aims of this research were to examine electrogenic i ntestinal secretion, in vitro, caused by the supernatants from macrophages stimulated with microcystin-LR, as well as to investigate the presence of i nterleukin-1 beta and tumour necrosis factor-alpha in these supernatants. W e found that the supernatants of macrophages stimulated with microcystin-LR (0.1, 0.3 and 1.0 mu g/ml) caused electrogenic intestinal effects (change in short-circuit currents (Delta SCC) = 57.6, 50.8 and 73.3, respectively, versus control = 19.6 mu A.cm(-2)) in a time-dependent way (microcystin-LR (1.0 mu g/ml) = 63.2, 108.8, 120.4 and 132.3 mu A.cm(-2) at time 0, 40, 50 and 60 min., respectively). In addition, the intestinal secretory activity present in these supernatants was blocked (57%) by the prior treatment of m acrophages with dexamethasone. We also demonstrated that microcystin-LR (0. 1, 0.3 and 1.0 mu g/ml) is capable of stimulating the synthesis of tumour n ecrosis factor-alpha (375.4, 369.0 and 610.8 pg/ml, respectively, versus co ntrol = 165.0 pg/ml) and interleukin-1 beta (198.9, 189.3 and 522.1 pg/ml, respectively, versus control = 39.7 pg/ml). These findings demonstrate that microcystin-LR induces the release of interleukin-1 beta and tumour necros is factor-alpha by peritoneal macrophages in vitro, and that the supernatan ts from these macrophages induce electrogenic secretion in rabbit ileal muc osa.