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 facto r (NGF) influences neuronal survival, differentiation and recovery fol lowing insult. 2 The effect of NGF upon human placental mast cells (HP MC) was investigated, since it is known that rodent mast cells express a functional receptor for NGF and secrete histamine upon challenge wi th this neurotrophic factor. Furthermore, human placental tissue conta ins a significant amount of NGF and expresses a NGF receptor. 3 HPMC w ere shown to secrete histamine in a concentration dependent manner in response to NGF (0.001-10.0 mu g ml(-1)) in the presence of the lipid cofactor phosphatidylserine (10.0 mu g ml(-1)). 4 NGF induced histamin e release from isolated HPMC with an EC(50) of 0.1 mu g ml(-1) NGF and maximal secretion of total cellular histamine of 22.3 +/- 3.4% at 3.0 mu g ml(-1). 5 The response was shown to be a secretory process, depe ndent upon the presence of exogenous calcium ions and to be pH- and te mperature-sensitive. 6 HPMC are suggested to be a suitable primary cel l model for use in aspects of in vitro toxicity testing, in terms of a ssessing the neuro-immunotoxic potential of neurotrophic therapeutics. In addition, mechanistic studies concerning those xenobiotics which m ay exert their neurotoxic effect via interaction with neurotrophic fac tors and, or their receptors, may be studied in this human cell model.