Human placental mast cells as an in vitro model system in aspects of neuro-immunotoxicity testing

1. In both the developing and adult nervous systems, nerve growth factor (NGF) influences neuronal survival, differentiation and recovery following insult. 2. The effect of NGF upon human placental mast cells (HPMC) was investigated, since it is known that rodent mast cells express a functional receptor for NGF and secrete histamine upon challenge with this neurotrophic factor. Furthermore, human placental tissue contains a significant amount of NGF and expresses a NGF receptor. 3. HPMC were shown to secrete histamine in a concentration dependent manner in response to NGF (0.001-10.0 micrograms ml-1) in the presence of the lipid cofactor phosphatidylserine (10.0 micrograms ml-1). 4. NGF induced histamine release from isolated HPMC with an EC50 of 0.1 microgram ml-1 NGF and maximal secretion of total cellular histamine of 22.3 +/- 3.4% at 3.0 micrograms ml-1. 5. The response was shown to be a secretory process, dependent upon the presence of exogenous calcium ions and to be pH- and temperature-sensitive. 6. HPMC are suggested to be a suitable primary cell model for use in aspects of in vitro toxicity testing, in terms of assessing the neuro-immunotoxic potential of neurotrophic therapeutics. In addition, mechanistic studies concerning those xenobiotics which may exert their neurotoxic effect via interaction with neurotrophic factors and, or their receptors, may be studied in this human cell model.