Synaptophysin: A novel marker for human and rat hepatic stellate cells

Synaptophysin is a protein involved in neurotransmitter exocytosis and is a neuroendocrine marker. We studied synaptophysin immunohistochemical expres sion in 35 human liver specimens (normal and different pathological conditi ons), in rat models of galactosamine hepatitis and carbon tetrachloride-ind uced cirrhosis, and in freshly isolated rat stellate cells. Synaptophysin r eactivity was present in perisinusoidal stellate cells in both human and ra t normal liver biopsies. The number of synaptophysin-reactive perisinusoida l cells increased in pathological conditions. Double staining for cu-smooth muscle actin and synaptophysin, detected by confocal laser scanning micros copy, unequivocally demonstrated colocalization of both markers in lobular stellate cells. In addition, freshly isolated rat stellate cells expressed synaptophysin mRNA (detected by polymerase chain reaction) and protein. Fin ally, electron microscopy showed the presence of small electron translucent vesicles, comparable to the synaptophysin-reactive synaptic vesicles in ne urons, in stellate cell projections. We conclude that synaptophysin is a no vel marker for quiescent as well as activated hepatic stellate cells. Toget her with the stellate cell's expression of neural cell adhesion molecule, g lial fibrillary acidic protein, and nestin, this finding raises questions a bout its embryonic origin and its differentiation. In addition, the presenc e of synaptic vesicles in stellate cell processes suggests a hitherto unkno wn mechanism of interaction with neighboring cells.