Lysophosphatidylserine potentiates nerve growth factor-induced differentiation of PC12 cells

Abstract

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 μg/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 μg/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.