Neurokinin-1 receptor signalling impacts bone marrow repopulation efficiency

PLoS One. 2013;8(3):e58787. doi: 10.1371/journal.pone.0058787. Epub 2013 Mar 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / metabolism*
  • Cell Lineage
  • Female
  • Gene Knockout Techniques
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Protein Precursors / deficiency
  • Receptors, Neurokinin-1 / deficiency
  • Receptors, Neurokinin-1 / genetics
  • Receptors, Neurokinin-1 / metabolism*
  • Signal Transduction*
  • Substance P / deficiency
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism
  • Tachykinins / deficiency

Substances

  • Protein Precursors
  • Receptors, Neurokinin-1
  • Tac4 protein, mouse
  • Tachykinins
  • Substance P