title: Neuropeptide control of bone marrow neutrophil production is mediated by both direct and indirect effects on CFU-GM.
abstract: Noradrenaline- and peptide-containing nerve fibres project into the bone marrow and terminate in association with stromal cells and within the parenchyma. Peptidergic nerve terminals are also associated with antigen-processing and -presenting cells throughout the body and have been shown to be important in leucocyte trafficking and wound healing, as well as haemopoiesis. Here, we tested the in vivo effects of deleting the peripheral neuropeptide network on haemopoiesis and also investigated whether the target cell population for these substances was myeloid progenitor cells (colony-forming unit-granulocyte/macrophage, CFU-GM). Deletion of the neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) by capsaicin abrogates normal blood cell production. These neuropeptides produced significant stimulation of colony formation from unfractionated bone marrow and elicited production of soluble factors capable of stimulating highly enriched CFU-GM. CGRP also had a direct stimulatory effect on highly enriched CFU-GM. Noradrenaline elicited factors that inhibited colony formation and had no direct effect on CFU-GM. We conclude that the neuropeptides form the positive arm of a neural control system and that noradrenaline acts as a negative regulator.
authors.affiliation: Neuroscience and Cell Biology Research Group, Department of Biomolecular Sciences, University of Manchester Institute of Science & Technology, Manchester, UK.
authors.forename: C S
authors.initials: CS
authors.lastname: Broome
authors.forename: A D
authors.initials: AD
authors.lastname: Whetton
authors.forename: J A
authors.initials: JA
authors.lastname: Miyan
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D016207:Cytokines / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D008297:Male; D051379:Mice; D009479:Neuropeptides / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology*; D009638:Norepinephrine / Q000502:physiology; D013373:Substance P / Q000502:physiology
chemical_list: D016207:Cytokines; D009479:Neuropeptides; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D009638:Norepinephrine