Abstract
Substance P (SP) is a neuropeptide which has been reported to have immunomodulatory activity. Most studies on SP have been performed on cells of the peripheral immune system. More recently, SP has been reported to have stimulatory activity on human bone marrow cells in vitro, and this activity was dependent on the presence of an adherent layer of cells. The in vitro adherent layer represents the stromal cells of the marrow. In this study, we directly addressed the effect of SP on cultured bone marrow stromal cells. Since stromal cells play an important role in the regulation of hematopoiesis, interactions of neuropeptides such as SP with this cell population could lead to an alteration of stem cell development within the bone marrow. Previously we have shown that SP stimulates protein synthesis in this cell population with two waves of protein synthesis activation, after 2 hr and 48 hr of SP incubation. In this study, we asked whether levels of known stromal cell cytokines were altered in response to SP incubation. We assayed the levels of Interleukin-7 (IL-7) and Stem Cell Factor (SCF) associated with the stromal cell surface following 2 hr and 48 hr of SP incubation. Cells were stimulated with SP for 2 hr or 48 hr. Following SP incubation, cells were washed and the levels of cell associated cytokine was determined by ELISA. Following 2 hr of treatment, 0.1 nM of SP significantly increased (p = 0.05) the level of IL-7 as compared to untreated controls. After 48 hr of treatment, 1, 10, and 100 nM SP significantly increased the levels of IL-7 in this cell population. When SCF levels were assayed, SP at all concentrations tested was found to increase significantly the levels of SCF following 2 hr of incubation. Following 48 hr of incubation, 10 and 100 nM of SP significantly increased the levels of SCF. The ability of SP to affect cytokine levels varied with time. Following 2 hr of SP incubation, cytokine levels were enhanced at the lower end of the concentration range as compared to 48 hr of SP treatment. A 48 hr incubation with SP yielded the highest levels of cytokine at the higher end of the concentration range. Taken together, the results of these studies suggest that SP has an immunoregulatory effect on bone marrow stromal cells leading to alteration in the production and/or secretion of regulatory cytokines such as IL-7 and SCF.
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References
Korneva, E.A., and L.M. Khai. 1964. Effect of destruction of hypothalmic areas on immunogenesis. Fed. Proc. Trans. Suppl. 23: T88.
Macris, N.T., R.C. Schiavi, M.S., Camerino, and M. Stein. 1970 Effect of hypothalmic lesions on immune processes in the guinea pig. Am. J. Physiol. 219: 1205.
McCain, H.W., I.B. Lamster, J.M. Bozzone, and J.T. Gribic. 1982. B-endorphin modulates human immune activity via nonopiate receptor mechanisms. Life Sci. 31: 1619.
Johnson, H.M., E.M. Smith, B.A. Torres, and J.E. Blalock. 1982. Regulation of the in vitro response by neuroendocrine hormones. Proc. Natl. Acad. Sci. USA 79: 4171.
Pernow, B. 1983. Substance P. Pharmacol. Rev. 35: 85.
Payan, D.G. 1989. Substance P: A modulator of neuroendocrine-immune function. Hosp. Pract. 24: 67.
Strand, F.L., J. Kenneth, R. Lisa, A.Z. Lisa, K. June, E.A. Stephan, J.A. Francis, and Y.G. Lara. 1991. Neuropeptide hormones as neurotrophic factors. Pharmacol. Rev. 71: 1017.
Payan, D.G., and E.J. Goetzl. 1985. Modulation of lymphocyte function by sensory neuropeptides. J. Immunol. 135: 783.
Pascual, D., J. Xu-Amano, H. Kiyono, J.R. McGhee, and K.L. Bost. 1991. Substance P acts directly on cloned B lymphoma cells to enhance IgA and IgM production. J. Immunol. 146: 2130.
Shanahan, F., J.A. Denburg, J. Fox, J. Bienenstock, and D. Befus. 1985. Mast cell heterogeneity: effects of neuroenteric peptides on histamine release. J. Immunol. 135: 1331.
Lotz, M., D.A. Carson, and J.H. Vaughan. 1987. Substance P activation of rheumatoid synoviocytes: neural pathway in pathogenesis of arthritis. Science 235: 893.
Hartung, H.P, K. Wolters, and K.V. Toyker. 1986. Substance P: binding properties and studies on cellular responses in guinea pig macrophages. J. Immunol. 136: 3856.
Moore, T.C., J.L. Lami,. and C.H. Spruck. 1989. Substance P increases lymphocytes traffic and lymph flow through peripheral lymph nodes of sheep. J. Immunol. 67: 109.
Calvo, C.F., G. Cavanel, and A. Senik. 1992. Substance P enhances IL-2 expression in activated human T-cells. J. Immunol. 148: 3498.
Laurenzi, A.M., M.A.A. Person, C. Dalsgaard, and A. Hoegerstrand. 1990. The neuropeptide substance P stimulates production of interleukin-1 in human blood monocytes: activated cells are preferentially influenced by the neuropeptide. Scand. J. Immunol. 31: 529.
Kimball, E.S., F.J. Persico, and J.L. Vaught. 1988. Substance P, neurokininA, and neurokinin B induce generation of IL-1-like activity in P388D1 cells. J. Immunol. 141: 3564
Wagner, F., R. Fink, R. Hart, and H. Dancygier. 1987. Substance P enhances interferon production by human peripheral blood mononuclear cells. Regul. Pept. 19: 355.
Rameshwar, P., D. Ganea, and P. Gascon. 1993. In vitro stimulatory effect of substance P on hematopoiesis. Blood 81: 391.
Dexter, T.M., T.D. Allen, and L.G. Lajtha. 1977. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J. Cell Physiol. 91: 335.
Perkins, S., and R.A. Fleischman. 1990. Hematopoietic microenviroment: origin, lineage, and transplant-ability of the stromal cells in long-term bone marrow cultures from chimeric mice. Blood 75, 620.
Pascual, D.W., and K. L. Bost. 1990. Substance P production by macrophage cell lines: a possible autocrine function for this neuropeptide. Immunology 71: 52.
Nilsson, J., M.A. von Euler, and C.J. Dalsgaard. 1985. Stimulation of connective tissue cell growth by Substance P and Substance K. Nature 315: 61.
Nakanishi, S. 1991. Mammalian tachykinin receptors. Annu. Rev. Neuroscience 14: 123.
Namen, A.E., A.E. Schmierer, C.J. March, R.W. Overell, L.S. Park, D.L. Urdal, and D.Y. Mochizuki. 1988. B cell precursor growth-promoting activity: purification and characterization of a growth factor active on lymphocyte precursors. J. Exp. Med. 167: 988.
Namen, A.E, S. Lupton, K. Hjerrild, J. Wignall, D.Y. Mochizuki, A. Schmierer, B. Mosley, C.J. March, D. Urdahl, S. Gillis, D. Cosman, and R.G Goodwin. 1988. Stimulation of B cell progenitors by cloned murine IL-7. Nature 333: 571.
Morrissey, P.J., R.G. Goodwin, R.P. Nordan, D. Anderson, K.H. Grabstein, D. Cosman, J. Sims, S. Lupton, B. Acres, S.G. Reed, D. Mochizuki, J. Eisenman, PJ Conlon, and A.E. Namen. 1989. Recominmbinant IL-7, pre-B cell growth factor, has co-stimulatory activity on purified mature T cells. J. Exp. Med. 169: 707.
Grabstein, K.H., A.E. Namen, K. Shanebeck, R.F. Voice, S.G. Reed, and M.B. Widmer. 1990. Regulation of T cell proliferation by IL-7. J. Immunol. 144: 3015.
Conlon, P.J., P.J. Morrissey, R.P.Nordan, K.H. Grabstein, K.S. Prickett, S.G. Reed, R. Goodwin, D. Cosman, and A.E. Namen. 1989. Murine thymocytes proliferate in direct response to Interleukin-7. Blood 74: 1368.
Quesenberrry, P.J., S. Rudnick, and D.C. Dale. 1991. Hematopoietic growth factors. Blood suppl (Hematology 1991, Education program: ASH meetings) p. 80.
Zsebo. K.M., J. Wypych, I.K. McNiece, H.S. Lu, K.A. Smith, S.B. Karkare, R.K. Sachdev, V.N. Yuschenkoff, N.C. Birkett, L.R. Williams, V.N. Satyagal, T. Weifong, R.A. Bosselman, E.A. Mendiaz, and K.E. Langley. 1990 Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver-conditioned medium. Cell 63: 213.
Witte, O.N. 1990. Steel locus defines new multipotent grwoth factor. Cell 63: 5.
Huang, E., K. Nocka, D.R. Beier, T-Y. Chu, J. Buck, H-W. Lahm, D. Wellner, P. Leder, and P. Besmer. 1990. The hematopoietic growth factor KL is encoded by the Si locus and is the ligand for c-kit tyrosine kinase receptor. Cell 63: 225.
Flanagan, J.G., and P. Leder. 1990. The kit ligand: a cell surface molecule altered in steel mutant fibroblasts. Cell 63: 185.
Allen, T.D., T.M. Dexter, and P.J Simmons. 1990. Marrow biology and stem cells. in: Colony-Stimulating Factors: Molecular and Cell Biology. (Dexter, T.M., Garland, J.M. and Testa, N.G. ed.) p.1, Marcel Dekker, Inc., New York.
Pamet, P., Payan, D.G., Kerdelhue, B., and Mitsuhashi, M. 1990. Neuroendocrine interaction on lymphocytes: testosterone-induced modulation of the lymphocyte Substance P receptor. J. Neuroimmunology. 28: 185.
Gordon, M.Y., G.P. Riley, S.M. Watt, and M.F. Greaves. 1987. Compartmentalization of a haematopoietic growth factor (GM-CSF) by glycosaminoglycans in the bone marrow microenvironment. Nature 326: 403.
Maggio, J.E. 1988. Tachykinins. Annu. Rev. Neurosci. 11:13.
Regoli, D.G. G. Drapeau, S. Dion, and P. D’Orleans-Juste. 1989. Receptors for substance P and related neurokinins Pharmacology. 38: 1.
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Manske, J.M., Sullivan, E.L., Andersen, S.M. (1995). Substance P Mediated Stimulation of Cytokine Levels in Cultured Murine Bone Marrow Stromal Cells. In: Atassi, M.Z., Bixler, G.S. (eds) Immunobiology of Proteins and Peptides VIII. Advances in Experimental Medicine and Biology, vol 383. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1891-4_7
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DOI: https://doi.org/10.1007/978-1-4615-1891-4_7
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