Human bone marrow angiogenesis: in vitro modulation by substance P and neurokinin A

Abstract

Summary. We have previously described a culture system for human bone marrow endothelial cells that organize into capillary tubes associated to pericytes. In the present work, we used this model to assess the angiogenic properties of tachykinins, which have been demonstrated to be involved in neuro-immuno-haematopoietic interactions. The substance P (SP) and neurokinin A (NKA) were similarly potent at increasing in vitro angiogenesis, via NK1 and NK2 receptors respectively. These mediators were not produced by cells in culture, suggesting that in vivo they may be released by nerve fibres in the bone marrow. Therefore, we looked for in situ innervation of the human bone marrow, unknown to date, using immunohistochemistry techniques. As in rodents, arterioles were largely innervated, associated with between one and 10 nerve fibres. Capillary innervation was more restrictive as a unique thin nerve fibre was found in the vicinity of only 6% of these vessels. Finally, no nerve fibres were observed in the vicinity of sinus walls. In conclusion, both in vitro results and the anatomical display of nerve fibres suggest a role in human bone marrow for the vasoactive neuropeptides SP and NKA, which were secreted into a perivascular location. These neural mediators might modulate blood flow in the bone marrow both in the short term by adjusting vascular tone and in the long term by inducing angiogenesis.

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

“…Data on innervation of human haematopoietic bone marrow is sparse. Recently, Pelletier et al (2002) demonstrated synaptophysin‐containing nerve fibres close to human bone marrow blood vessels, but no fibres were detected among marrow parenchymal cells, i.e. in the haematopoietic compartment.…”

“…Although the presence of nerves within the bone marrow parenchyma of rodents is fairly well established, firm evidence for their presence is apparently lacking for humans (Pelletier et al , 2002). Therefore, the second intention of the present study was to clarify the existence of human bone marrow innervation.…”

Transformation of breast cells by truncated neurokinin-1 receptor is secondary to activation by preprotachykinin-A peptides

“…Despite this limit, the present studies serve as an impetus for continued research to treat BCCs at the level of cell membrane with antagonists and intracellularly to examine mediators of cytokines induced by NK1-Tr receptor ( Table 2). Because PPT-A peptides could directly and indirectly act as angiogenic factors, targeting NK1-Tr might lead to decrease angiogenesis (26,27).…”

Endothelial progenitor cells in pterygium pathogenesis

“…[11][12][13][14] Evidence suggests that VEGF is a potent endothelial cell-specific factor, and VEGF has been demonstrated to have a chemotactic effect on EPCs, whereas SCF (also called c-kit ligand) is a multi-potent growth factor that targets diverse haematopoietic cells including stem cells. 13,15 Another modulating factor, SP (a neurotransmitter), has been reported to be involved in angiogenesis and neuroimmunohaematopoietic interactions, 16,17 and in corneal wound healing. 18,19 Previous reports indicate that these stem cell-modulating factors are expressed in pterygium.…”