Is the human haematopoietic bone marrow innervated?
Research field:Autonomic nervous system
Authors:Nicolaysen A, Benestad HB, Njå A, Iversen PO
Address of presenting
author:		Dept. of Physiology, University of Oslo
E-mail:anne.nicolaysen@basalmed.uio.no
Phone:47 22 85 12 26
Fax:47 22 85 12 49
Text of abstract Introduction
There is firm evidence that the murine bone marrow is innervated with fibres terminating in close proximity to vascular, stromal and haematopoietic progenitor cells (Benestad et al. 1998a and references therein). Despite this, we failed to detect any definite regulatory functions to these neurons (Iversen, 1997; Benestad et al. 1998a). However, these negative data have been challenged (Maestroni, 1998; Miyan et al. 1998; Benestad et al. 1998b). While these apparent discrepancies might partly be explained by various experimental approaches, species differences could not be excluded. It was therefore of interest to examine whether the human haematopoietic bone marrow is supplied with nerve fibres. To the best of knowledge there is no clear experimental evidence to date that such innervation exists.

Methods
Following written consent, bone marrow biopsies were collected from the iliac crest of two healthy donors and using standard techniques. For comparisons, we also studied resection specimen from the human gut wall of one patient, as well as bone marrow samples and irides from mice. Human preparations were frozen in isopenthane/dryice and cryostate-sections were stained with glyocxylic acid or prepared for immunohistochemistry with anti-thyrosine hydroxylase antibody and anti-neurofilament antibody. Fresh irides and smears made from marrow plugs washed out of the tibiae were treated identically to the frozen sections.

Results
We could with glyocxylic acid demonstrate nor-epinephrine containing nerve fibres in all four preparations. Nerve fibres containing thyrosine hydroxylase were detected in irides and human gut wall, but not in mouse or human bone marrow. With anti-neurofilament antibody bundles of nerve fibers were seen in all preparations except in the human bone marrow.

Conclusions
These preliminary data indicate that at least the human bone marrow is innervated with nor-epinephrine containing terminals, probably of sympathetic origin. The possible regulatory role of these neurons is unknown and merits further investigation.

References
Benestad, H.B., Strøm-Gundersen, I., Iversen, P.O., Haug, E. & Njå, A. 1998a. Blood 91: 1280-1287
Benstad, H.B., Iversen, P.O. & Njå, A. 1998b. Blood 92: 2972-2973
Iversen, P.O. 1997. Acta Physiol Scand 159: 269-276
Maestroni, G.J.M. 1998. Blood 92: 2971.
Miyan, J.A., Broome, C.S. & Whetton, A.D. 1998. Blood 92: 2971-2972.

Keywords:bone marrow, human, innervation, murine

Created 2000-04-28