Neurokinin-1 Receptor Signalling Impacts Bone Marrow Repopulation Efficiency |
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| Authors: | Alexandra Berger Catherine Frelin Divya K Shah Patricia Benveniste Robert Herrington Norma P Gerard Juan-Carlos Zú?iga-Pflücker Norman N Iscove Christopher J Paige |
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| Institution: | 1. Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.; 2. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.; 3. Department of Immunology, University of Toronto, Toronto, Ontario, Canada.; 4. Sunnybrook Research Institute, Toronto, Ontario, Canada.; 5. Ina Sue Perlmutter Laboratory, Children''s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.; Emory University, United States of America, |
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| 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. |
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