Nerve growth factor-induced neurite outgrowth from normal human chromaffin cells
Tischler, A.S.; Delellis, R.A.; Biales, B.; Nunnemacher, G.; Carabba, V.; Wolfe, H.J.
Laboratory Investigation; a Journal of Technical Methods and Pathology 43(5): 399-409
1980
ISSN/ISBN: 0023-6837 PMID: 6252370 Document Number: 157786
Human and rat pheochromocytoma cells in culture form processes in response to nerve growth factor (NGF). To determine whether capacity for process outgrowth is a characteristic of normal as well as neoplastic chromaffin cells, enzymatically dissociated cells from normal adult human adrenal medullas were maintained in monolayer cultures for up to 6 wk. Many chromaffin cells in all of the cultures formed neurite-like processes in response to NGF, and a smaller number spontaneously formed processes. Quantitative increases in percentage of cells with processes and mean process length in NGF-treated cultures were statistically significant. NGF-induced process formation was diminished, but not completely abolished by 10-5 M dexamethasone. Process-forming cells contained secretory granules of low, high and intermediate electron densities, resembling granules seen in epinephrine and norepinephrine-producing adrenal medullary cells in vivo. In early stages of process formation, numerous granules and brilliant formaldehyde-induced fluorescence indicative of catecholamine stores could be observed in cell bodies of process-forming cells. In later stages, there was a marked diminution of formaldehyde-induced fluorescence and a decreased number of granules in cell bodies, except in occasional cells which appeared to be surrounded by other cells within cell clusters. Processes of NGF-treated cells accumulated large numbers of 30-160 nm granules and of 30-70 nm synaptic-like vesicles resembling those in adrenergic and cholinergic neurons, but no synapses were observed. Morphologic and cytochemical changes similar to those in the present study were previously reported in cultures of NGF-treated human and rat pheochromocytoma cells. Some of the plasticity exhibited by pheochromocytoma cells therefore probably reflects pluripotency retained by normal mature chromaffin cells, rather than a unique manifestation of neoplasia. The normal adrenal medulla may contain subpopulations of chromaffin cells with varied responsiveness to NGF and steroids.