Dynamic norepinephrine alterations in bone marrow: evidence of functional innervation

Efferent sympathetic nerve activity has been hypothesized to regulate the proliferation and maturation of leukocytes in the bone marrow. Although there is histological evidence for bone marrow innervation and documentation of measurable neurotransmitter, functional activation of these nerves to external stimulation has never been demonstrated. The present study was designed to assess the dynamics of norepinephrine (NE) release in bone marrow in response to well-established protocols known to elevate sympathetic activity. Toward this end, norepinephrine turnover was measured using isotopic and non-isotopic methods in mice in response to cold exposure and bacterial challenge. Cold exposure increased NE turnover rate in bone marrow by 36% from 0.33 to 0.45 ng g(-1) h(-1), while peritoneal Pseudomonas aeruginosa infection increased bone marrow NE turnover rate by 131% from 0.13 to 0.30 ng g(-1) h(-1). These results demonstrate that the adrenergic innervation of the bone marrow is functionally dynamic and is responsive to generalized stress. Furthermore, these results lend credence to the premise that neural mechanisms participate in regulation of lympho- and myelopoietic cellular events.