No Neuronal Regulation of Murine Bone Marrow Function

Abstract

Bone marrow is innervated by efferent (sympathetic) and afferent nerves, but it is not clear whether these nerves affect cell formation or release in any significant way. To elucidate this problem, we studied mice neonatally sympathectomized with 6-hydroxydopamine and adult mice in which one hind limb was surgically denervated. Progenitor and transit cell numbers and proliferative activity were estimated in bone marrow, blood, and spleen. In addition, we performed unilateral electrical stimulation of nerve fibers to tibial marrow and applied a cell mobilizing stimulus (bleeding, granulocyte colony-stimulating factor injection, or intraperitoneal injection of a chemotactic substance) to investigate cell egress from the marrow. Blood flow to hindleg bone marrow was assessed with the radioactive microsphere technique. Except for a smaller bone marrow cell population and lower body weight in neonatally sympathectomized mice, we found no clear indications that bone marrow innervation influenced cell production. Also, the innervation did not detectably affect cell release from the marrow. Electrical stimulation of hind limb nerves did not change the blood flow to the marrow, whereas it markedly decreased blood flow to the overlying muscle. We therefore conclude that no obvious function can be ascribed to tibial marrow innervation in the mouse.

Preserved granulocyte formation and function, as well as bone marrow innervation, in subjects with complete spinal cord injury

“…The presence of cognate receptors for neuronal transmitters on bone marrow cells supports this notion (Maestroni & Conti, 1994;Rameshwar & Gascon, 1995;. Surprisingly therefore, we could not demonstrate any function of innervation on mouse tibial bone marrow function, by denervation, electrical nerve stimulation or neonatal chemical sympathectomy (Benestad et al, 1998a). However, these findings have been challenged on methodological grounds (Maestroni, 1998;Miyan et al, 1998a).…”

“…The irides were mounted on coated glass slides. Smears were made from marrow plugs (Benestad et al, 1998a). These preparations were immediately processed for glyoxylic acid-induced fluorescence or immunohistochemistry with antibodies.…”

Blood flow to the haemopoietic bone marrow

“…Chemical denervation of the sympathetic nervous system with 6-hydroxydopamine did not a¡ect marrow blood £ow either (Iversen et al 1994a). Moreover, sympathetic denervation did not change either marrow metabolism (Iversen & Skrede 1994) or cellular di¡erentiation and subsequent marrow release of leucocytes (Benestad et al 1991). In contrast, stimulation of isolated carotid sinus baroreceptors augmented marrow blood £ow in the anaesthetized dog, while activation of sympathetic pathways by baroreceptor dea¡erentation in anaesthetized cats decreased marrow blood £ow (Gross et al 1979).…”

Macrophage‐dependent regulation of neutrophil mobilization and chemotaxis during development of sterile peritonitis in the rat

“…This indicates that the mobilization of neutrophils from the bone marrow might be dependent on specific macrophage signaling, or the concentration of humoral factors must exceed a threshold to achieve mobilization. The mobilizing signal to the bone marrow is probably of humoral origin, since we previously found that production and release of neutrophils from the bone marrow during the development of a sterile peritonitis in mice did not depend on the innervation of the marrow (24). Surprisingly, the mobilization of neutrophils to the blood was apparently not affected early in the inflammatory process, since the 5 hours neutrophil blood concentration was not significantly different in macrophage‐depleted and control rats.…”