Neurokinin-1 Receptor Signalling Impacts Bone Marrow Repopulation Efficiency

作者：Berger Alexandra; Frelin Catherine; Shah Divya K; Benveniste Patricia; Herrington Robert; Gerard Norma P; Zuniga Pfluecker Juan Carlos; Iscove Norman N; Paige Christopher J^*

来源：PLos One, 2013, 8(3): e58787.

DOI：10.1371/journal.pone.0058787

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.

• 出版日期2013-3-14