Journal of Neuroscience, Vol 15, 5892-5899, Copyright © 1995 by Society for Neuroscience
NGF modulates sympathetic innervation of lymphoid tissues
SL Carlson, KM Albers, DJ Beiting, M Parish, JM Conner and BM Davis
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington 40536-0084, USA.
Immune tissues are known to be innervated by the sympathetic nervous
system, but little is known of what directs the innervation to specific
tissue compartments. This report examines the sympathetic innervation of
immune tissues in transgenic mice that overexpress nerve growth factor
(NGF) in skin and other epithelial structures. NGF transgenic mice
exhibited dramatic hyperinnervation in the splenic marginal zone, and the
medulla and capsule of peripheral lymph nodes. In contrast, the transgenic
mesenteric lymph nodes showed no hyperinnervation. This difference
correlated with the location of these nodes; peripheral lymph nodes drain
skin where the transgene was expressed while mesenteric lymph nodes drain
non-transgene-expressing structures. In addition, the level of innervation
correlated with the level of NGF peptide content as assayed by ELISA (3-
and 13-fold increase in transgenic spleen and axillary lymph nodes,
respectively; no increase in mesenteric nodes) and immunocytochemistry.
RT-PCR showed that the NGF transgene was not being expressed in the immune
tissues, suggesting that immune tissues can concentrate transgene-produced
NGF. It was also demonstrated that the change in innervation had functional
consequences. The mitogen response to concanavalin A (ConA) by spleen cells
was decreased in the transgenics suggesting that elevated catecholamines or
NGF can modulate the proliferative response of these cells. These mice
demonstrate that NGF can modulate the sympathetic innervation and function
of the immune system.
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