Lysophosphatidylserine potentiates nerve growth factor-induced differentiation of PC12 cells

Since lysophosphatidylserine (LPS) is required for nerve growth factor (NGF)-induced secretion of histamine from rat mast cells, we investigated whether LPS might potentiate the effects of NGF in inducing neural differentiation of PC12 cells. Cell morphology was evaluated 48 h after addition of NGF, LPS or NGF + LPS. LPS alone was ineffective, but strongly promoted NGF-induced differentiation to give rise to cells that more closely resembled neurons in primary culture. LPS increased the number of PC12 cells that developed neurites in response to NGF (0.01-40 ng/ml), with the response to 1.0 ng/ml increasing from 17.8 +/- 2.2 to 50.8 +/- 4.1% when LPS was also present. Neurite length was also greater in PC12 cells receiving NGF + LPS: 17.8 +/- 2.2% of cells had neurites longer than three cell body diameters with 1.0 ng/ml NGF + 1 microg/ml LPS, compared to 1.6 +/- 1.6% with NGF alone. Further, cells responding to NGF + LPS typically developed only 1-2 neurites per cell (90.9%, 1 microg/ml LPS), compared with the multipolar appearance with NGF alone (71.1% with 3-6 neurites, 10 ng/ml NGF). LPS occurs at sites of tissue damage where NGF can also be present, and therefore may be a naturally-occurring modifier of neuronal structure and/or function.