title: Neurokinin-1 receptor signalling impacts bone marrow repopulation efficiency.
abstract: Tachykinins are a large group of neuropeptides with both central and peripheral activity. Despite the increasing number of studies reporting a growth supportive effect of tachykinin peptides in various in vitro stem cell systems, it remains unclear whether these findings are applicable in vivo. To determine how neurokinin-1 receptor (NK-1R) deficient hematopoietic stem cells would behave in a normal in vivo environment, we tested their reconstitution efficiency using competitive bone marrow repopulation assays. We show here that bone marrow taken from NK-1R deficient mice (Tacr1(-/-)) showed lineage specific B and T cell engraftment deficits compared to wild-type competitor bone marrow cells, providing evidence for an involvement of NK-1R signalling in adult hematopoiesis. Tachykinin knockout mice lacking the peptides SP and/or HK-1 (Tac1 (-/-), Tac4 (-/-) and Tac1 (-/-)/Tac4 (-/-) mice) repopulated a lethally irradiated wild-type host with similar efficiency as competing wild-type bone marrow. The difference between peptide and receptor deficient mice indicates a paracrine and/or endocrine mechanism of action rather than autocrine signalling, as tachykinin peptides are supplied by the host environment.
authors.affiliation: Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Berger
authors.forename: Catherine
authors.initials: C
authors.lastname: Frelin
authors.forename: Divya K
authors.initials: DK
authors.lastname: Shah
authors.forename: Patricia
authors.initials: P
authors.lastname: Benveniste
authors.forename: Robert
authors.initials: R
authors.lastname: Herrington
authors.forename: Norma P
authors.initials: NP
authors.lastname: Gerard
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Zúñiga-Pflücker
authors.forename: Norman N
authors.initials: NN
authors.lastname: Iscove
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Paige
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D019070:Cell Lineage; D005260:Female; D055786:Gene Knockout Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011498:Protein Precursors / Q000172:deficiency; D018040:Receptors, Neurokinin-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013373:Substance P / Q000172:deficiency; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D015320:Tachykinins / Q000172:deficiency
chemical_list: D011498:Protein Precursors; D018040:Receptors, Neurokinin-1; C423233:Tac4 protein, mouse; D015320:Tachykinins; D013373:Substance P