TOXICITY OF RICIN AND VOLKENSIN, 2 RIBOSOME-INACTIVATING PROTEINS, TOMICROGLIA, ASTROCYTE, AND NEURON CULTURES

Ricin and volkensin, two potent toxins belonging to the family of ribo some-inactivating proteins (RIPs), have been largely exploited in rece nt years in in vivo experiments of neuronal degeneration consequent to suicide transport or immunolesioning. We have determined both the tox icity of, and the inhibition of, protein synthesis by ricin and volken sin in in vitro cultures enriched in microglial cells, astrocytes, or neurons. In microglial cultures, 50% of toxicity (estimated by LDH rel eased from dead cells) after 24 h exposure to RIPs was obtained with v olkensin at 2.2x10(-12) M concentration and 50% of protein synthesis i nhibition at 2x10(-14) M concentration. Both values were higher by abo ut one order of magnitude in astrocyte-enriched cultures. Toxicity of, and inhibition of, protein synthesis by, ricin were lower for both ce ll types by about 1 order of magnitude as compared to volkensin. Cereb ellar granule neurons in culture survived remarkably well to 24 h expo sure to ricin or volkensin, although their protein synthesis was effec tively inhibited by the two toxins with a potency similar to that foun d for astrocytes. These results demonstrate that glial cells, in parti cular microglia, are very sensitive to RIPs toxicity and should, there fore, be a primary target of these toxins when injected in vivo. Thus, the damage observed after in vivo experiments could be partly related to diffusion of toxic substances from early-affected glial cells. (C) 1997 Wiley-Liss, Inc.