Rodent and human mast cells as an in vitro model in neuroimmunotoxicity testing

Mast cells derived from rodent or human tissues, either by direct lavage or following enzymic dispersal, secrete biogenic amines on challenge with a range of xenobiotics. In addition to synthetic pathways, re-uptake systems and metabolizing enzymes for histamine and 5-hydroxytryptamine, mast cells are responsive to neurotrophic factors, for example nerve growth factor (NGF). In these studies, rat peritoneal mast cells and human placental mast cells have been compared in terms of histamine 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 survival of populations of nerve cells in the peripheral and central nervous systems, potential neurotoxicants or exogenously applied growth factors 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 neuroimmunotoxicity testing for xenobiotics interfering with NGF function, for investigating the effects of neurotoxicants on monoamine function and for studying mechanistic aspects of neurodegenerative diseases.