RODENT AND HUMAN MAST-CELLS AS AN IN-VITRO MODEL IN NEUROIMMUNOTOXICITY TESTING

Mast cells derived from rodent or human tissues, either by direct lava ge or following enzymic dispersal, secrete biogenic amines on challeng e with a range of xenobiotics. In addition to synthetic pathways, re-u ptake systems and metabolizing enzymes for histamine and 5-hydroxytryp tamine, mast cells are responsive to neurotrophic factors, for example nerve growth factor (NGF). In these studies, rat peritoneal mast cell s and human placental mast cells have been compared in terms of histam ine release induced by a number of compounds. Of particular interest, it has been demonstrated that these mast cell populations functionally respond to NGF. Since NGF is essential to the development and surviva l of populations of nerve cells in the peripheral and central nervous systems, potential neurotoxicants or exogenously applied growth factor s may interact with this trophic factor and/or its receptor to produce apparent toxicity. It is suggested that mast cells may be a suitable primary cell model for use in aspects of in vitro neurotoxicity and ne uroimmunotoxicity testing for xenobiotics interfering with NGF functio n, for investigating the effects of neurotoxicants on monoamine functi on and for studying mechanistic aspects of neurodegenerative diseases.