Bone marrow innervation regulates cellular retention in the murine haemopoietic system

Abstract

Summary. An anatomical analysis of the innervation of murine femora revealed intimate association of haemopoietic and stromal cells with nerve fibres. The mechanical denervation of these femora resulted in significant mobilization of cells into the peripheral blood within 24 h. There was a decrease in femoral cellularity and analysis of the type of cells mobilized also revealed that there was an increase in progenitor cells in the peripheral blood. In non-splenectomized mice these progenitor cells were quickly cleared from the circulation. Chemical sympathectomy of mice with 6-hydroxydopamine resulted in decreased bone marrow cellularity without a change in bone marrow or peripheral blood progenitor cell numbers, nor the sustained rise in peripheral leucocytes observed with whole nerve denervation. These observations argue for selective control of mobilization by the nervous system and also indicate possible control of proliferation within the bone marrow. We conclude that the innervation has an important role in the maintenance of the blood-marrow interface, control of peripheral blood cell numbers, and mobilization of colony forming cells into the periphery.

Sympathetic modulation of immunity: Relevance to disease

“…Within 24 h after transecting the femoral nerve, or after chemical sympathectomy with 6-OHDA, bone marrow cellularity decreases [9]. This effect is due to the egress of mature and progenitor hematopoetic cells into the peripheral blood [9]. In another study, NE mobilized fat from the bone marrow [27].…”

“…Thus, noradrenergic (NA) influences on immunity, while still not entirely understood, have been the most extensively investigated. Neural regulation of immune function by peptide neurotransmitters that co-localize with NE, such as neuropeptide Y (NPY), adenosine triphosphate (ATP), opioid peptides, corticotropin-releasing hormone (CRH) and vasoactive NA nerves closely associate with hematopoietic and stromal cells in the bone marrow [2,[4][5][6][7][8][9]. Sympathetic nerve terminals directly appose periarterial adventitial cells, a particular type of stromal cell, that is an important source of growth factors and adhesion molecules [8].…”

Is Healing of Fractures Regulated Centrally?

“…The study also indicates a possible nervous control of cell proliferation within the bone marrow [4].…”

Preferential expression of the vasoactive intestinal peptide (VIP) receptor VPAC1 in human cord blood-derived CD34+CD38− cells: possible role of VIP as a growth-promoting factor for hematopoietic stem/progenitor cells

“…It has been suggested that nerve fibers contribute to the regulation of blood cell production, although there is some controversy about these findings. [41][42][43][44] Based on these findings taken together, it can be speculated that the growth-promoting effect of VIP on hematopoietic progenitor cells is exerted predominantly in the vicinity of VIP-producing nerve terminals in the BM microenvironment. How the growth-promoting effects of VIP contribute to the in vivo regulation of hematopoiesis remains unknown and should be investigated in future studies.…”