Margaret E. Checinski

The effect of chemical sympathectomy on natural killer cells in mice.

The nervous system affects immune regulation. We permanently ablated the sympathetic nervous system (SNS) of CBA mice with 6-OHDA at birth. Function of splenic natural killer (NK) cells in the sympathectomized mice was equivalent to controls at 2 weeks, but rose significantly above control levels at 4 weeks. NK cell function decreased below control values thereafter. NK cell numbers paralleled these changes in NK cell function. Our data suggest that the SNS may regulate the number and function of splenic NK cells during development.

Sympathetic nervous system and PC12 pheochromocytoma-derived factors suppress stimulation of lymphocytes

We have reported previously that ablation of the sympathetic nervous system augments immune responses in mice and rats. In the present study we show that a factor present in the sympathetic cervical ganglia of newborn rats suppresses Con A-induced stimulation of splenic T lymphocytes significantly whether added prior to, throughout, or following exposure to Con A. We also show that rat PC 12 pheochromocytoma cells secrete a factor which has the same inhibitory effect on T cell proliferation as the sympathetic ganglia-derived factor.

PC12 pheochromocytoma and sympathetic nervous system derived trophic factors augment growth of neuroblastoma.

A trophic factor secreted by PC12 rat pheochromocytoma augments growth of C1300 neuroblastoma clonal lines S20, N18 and C46, but does not affect growth of the NIE 115 line. A trophic factor present in newborn sympathetic ganglia has the same biological effect on neuroblastoma cell lines. PC12 cells and sympathetic ganglia are both of neural crest origin; possibly both secrete the same trophic factor.

Sympathetic nervous system and glioma growth

C-6 glioma cells possess beta-adrenergic receptors on the cell surface. Activation of beta-adrenergic receptors with beta-adrenergic agonists increases intracellular levels of cAMP and leads to differentiation of C-6 glioma cells in vitro. The present study shows that growth of C-6 glioma tumor in rats with ablated sympathetic nervous system is augmented as compared to controls. Lack of normal noradrenergic stimulation of C-6 glioma cells may lower intracellular cAMP and allow unrestricted growth of this tumor.