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The Role of Substance P in Cytokine Production by Glial Cells

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Book cover Biology and Pathology of Astrocyte-Neuron Interactions

Part of the book series: Altschul Symposia Series ((ALSS,volume 2))

Abstract

Substance P (SP), a neuropeptide released by peripheral sensory neurons, plays an important role in pain perception and acute inflammation (Sandberg and Iverson, 1982). It is also involved in peripheral autoimmune inflammatory diseases, most clearly with experimental adjuvant arthritis. Rats with adjuvant arthritis develop increased levels of SP in nerves innervating the arthritic joints, and depleting these animals of SP with capsaicin ameliorates the arthritis (Colpaert et al., 1983). Conversely, adding exogenous SP to the joint makes the arthritis more severe (Levine et al., 1984). Acute injury stimulates the release of SP (up to 2.8×10−15M into lymph) within 5–10 minutes (Jonsson et al., 1986). SP levels in blister fluid from infections, eczema, and bullous pemphigoid can be 3×10−11M (Wallengren et al., 1986), while SP in acute inflammatory exudates can be as much as 2×10−9M (Tissot et al., 1988), indicating high levels of SP secretion under these conditions. Inflammatory bowel disease tissue has a 1000-fold increase in SP receptors and is another instance where SP may be contributing to chronic inflammation (Mantyh et al., 1988).

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References

  • Adams, C.W.M., Abdulla, Y.H., Tomes, E.M., and Poston, R.N., 1987, Periventricular lesions in multiple sclerosis: their perivenous origin and relationship to granular ependymitis, Neuropath. Appl. Neurobiol. 13: 141.

    Article  CAS  Google Scholar 

  • Aggarwal, B.B., Kohr, W.J., Hass, P.E., Moffat, B., Spencer, S.A., Henzel, W.J., Bringman, T.S., Nedwin, G.E., Goeddel, D.V. and Harkins, R.N., 1985, Human tumor necrosis factor: production, purification, and characterization, J. Biol. Chem. 260: 2345.

    PubMed  CAS  Google Scholar 

  • Bailey, S.J., Featherstone, R.L., Jordan, C.C. and Morton, I.K.M., 1986, An examination of the pharmacology of two substance P antagonists and the evidence for tachykinin receptor subtypes, Brit. J. Pharmacol. 87: 79.

    Article  CAS  Google Scholar 

  • Bar-Shavit, Z., Goldman. R., Stabinski, Y., Gottlieb, P., Fridkin, M., Teichberg, V.I., and Blumberg, S., 1980, Enhancement of phagocytosis - a newly found activity of substance P residing in its N-terminal tetrapeptide sequence, J. Immunol. 130: 89.

    Google Scholar 

  • Beaujouan, J.C., Torrens, Y., Saffroy, M., and Glowinski, J., 1986, Quantitative autoradiographic analysis of the distribution of binding sites for 125E Bolton Hunter derivatives of eledoisin and substance P in the rat brain, Neurosci. 18: 857.

    Article  CAS  Google Scholar 

  • Brandwein, S.R., 1986, Regulation of interleukin-1 production by mouse peritoneal macrophages. Effects of arachidonic acid metabolites, cyclic nucleotides, and interferon, J. Biol. Chem. 261: 8624.

    PubMed  CAS  Google Scholar 

  • Broman, T., 1964, Blood-brain barrier damage in multiple sclerosis supravital test observations, Acta Neurol. Scand. 40 (Suppl. 10): 21.

    Article  Google Scholar 

  • Buck, S.H., Maurin, Y., Burks, T.F., and Yamamura, H.I., 1984, High-affinity 3H-substance P binding to longitudinal muscle membranes of the guinea pig small intestine, Life Sci. 34: 497.

    Article  PubMed  CAS  Google Scholar 

  • Burcher, E., and Buck, S.H., 1986, Multiple tachykinin binding sites in hamster, rat, and guinea pig urinary bladder, Eur. J. Pharmacol. 128: 165.

    Article  PubMed  CAS  Google Scholar 

  • Bynke, G., Hakanson, R., Horig, J., and Leander, S., 1983, Bradykinin contracts the pupillary sphincter and evokes ocular inflammation through release of neuronal substance P, Eur. J. Pharmacol. 91: 469.

    Article  PubMed  CAS  Google Scholar 

  • Carpenter, M.B., 1969, “Human Neuroanatomy,” The Williams and Wilkins Company, Baltimore.

    Google Scholar 

  • Cavender, D., Haskard, D., Yu, C-L., Iguchi, T., Miossec, P., Oppenheimer-Marks, N., and Ziff, M., 1987, Pathways to chronic inflammation in rheumatoid synovitis, FASEB J. 46: 113.

    CAS  Google Scholar 

  • Charles, A.C., Merrill, J.E., Dirksen, E.R., and Sanderson, M.J., 1991, Intercellular signaling in glial cells: calcium waves and oscillations in response to mechanical stimulation and gluatamate, Neuron 6: 983.

    Article  PubMed  CAS  Google Scholar 

  • Charles, A.C., Dirksen, E.R., Merrill, J.E., and Sanderson, M.J., Mechanisms of intercellular calcium signaling in glial cells studied with dantrolene and thapsigargin, Glia, in press.

    Google Scholar 

  • Colpaert, F.C., Donnerer,.J, and Lembeck, F., 1983, Effects of capsaicin on inflammation and on the substance P content of nervous tissue in rats with adjuvant arthritis, Life Sci. 32: 1827.

    CAS  Google Scholar 

  • Conlon, P.J., 1983, A rapid biologic assay for the detection of interleukin 1, J. Immunology 131: 1280.

    CAS  Google Scholar 

  • Conrad, G.W., and Rink, T.J., 1986, Platelet activating factor raises intracellular calcium ion concentration in macrophages, J. Cell Biol. 103: 439.

    Article  PubMed  CAS  Google Scholar 

  • Dinarello, C.A. and Savage, N., 1989, Interleukin-1 and its receptor, Crit. Rev. Immunol. 9: 1.

    PubMed  CAS  Google Scholar 

  • Edvinsson, L., McCulloch, J. and Uddman, R., 1982, Feline cerebral veins and arteries: comparison of autonomic innervation and vasomotor responses, J. Physiol. 325: 161.

    PubMed  CAS  Google Scholar 

  • Edvinsson, L., Cervos-Navarro, J., Larsson, L-I., Owman, C.H., and Ronnberg A-L., 1977, Regional distribution of mast cells containing histamine, dopamine, or 5-hydroxytryptamine in the mammalian brain, Neurol. 27: 878.

    Article  CAS  Google Scholar 

  • Fog, T., 1965, The topography of plaques in multiple sclerosis, Acta Neurol. Scand. 41 (Suppl. 15): 3.

    Google Scholar 

  • Frank, E., Pulver, M., and de Tribolet, N., 1986, Expression of class II major histocompatibility antigens on reactive astrocytes and endothelial cells within the gliosis surrounding metastases and abscesses, J. Neuroimmunol. 12: 29.

    Article  PubMed  CAS  Google Scholar 

  • Freemont AJ, and Ford WL: Functional and morphological changes in post capillary ventiles in relation to lymphocytic infiltration into BCG-induced granulomata in rat skin, J. Pathol. 147: 1.

    Google Scholar 

  • Graeber, M.B., Streit, W.J., Kiefer, R., Schoen, S.W., and Kreutzeberg, G.W., 1990, New expression of myelomonocytic antigens by microglia and perivascular cells following lethal motor neuron injury. J. Neuroimmunol. 27: 121.

    Article  PubMed  CAS  Google Scholar 

  • Hartung, H.-P., Heininger, K., Schafer, B., and Toyka, K.V., 1988, Substance P and astrocytes: stimulation of the cyclooxygenase pathway of arachidonic acid metabolism, FASEB J. 2: 48.

    PubMed  CAS  Google Scholar 

  • Hartung, H.-P., Wolters, K. and Toyka, K.V., 1986, Substance P: Binding properties and studies on cellular responses in guinea pig macrophages, J. Immunl. 136: 3856.

    CAS  Google Scholar 

  • Hashimoto, M., Ishikawa, Y., Yokota, S., Goto, F., Bando, T., Sakakibara, Y., and Iriki, M., 1991, Action site of circulating Interleukin-1 on the rabbit brain. Brain Res. 540: 217.

    Article  PubMed  CAS  Google Scholar 

  • Hofman, F.M., von Hanwehr, R.I., Dinarello, C.A., Mizel, S.B., Hinton, D., and Merrill, J.E., 1986, Immunoregulatory molecules and IL2 receptors identified in multiple sclerosis brain, J. Immunol. 136: 3239.

    PubMed  CAS  Google Scholar 

  • Itakura, T., Okuno, T., Nakakita, K., Kamei, I., Naka, Y., Nakai, K., Imai, H., Komai, N., Kimura, H., and Maeda, T., 1984, A light and electron microsopic immunohistochemical study of vasoactive intestinal polypeptide-and substance P-containing nerve fibers along the cerebral blood vessels: comparison with aminergic and cholinergic fibers, J. Cereb. Blood Flow Metabol. 4: 407.

    Article  CAS  Google Scholar 

  • Jonsson, C-E., Brodin, E., Dalsgaard, C-J., and Haegerstrand, A. 1986, Release of substance-P-like immunoreactivity in dog paw lymph after scalding injury, Acta Physiol. Scand., 126: 21.

    Article  PubMed  CAS  Google Scholar 

  • Kimball, E.S., Persico, F.J. and Vaught, J.L., 1988, Substance P, neurokinin A, and neurokinin B induce generation of IL-1-like activity in P388D1 Cells, J. Immunol. 141: 3564.

    PubMed  CAS  Google Scholar 

  • Kostyk, S.K., Kowall, N.W., and Hauser, S.L., 1989, Substance P immunoreactive astrocytes are present in multiple sclerosis plaques, Brain Res. 504: 284.

    Article  PubMed  CAS  Google Scholar 

  • Larsen, P.J., Mikkelsen, J.D., and Saermak, T., 1989, Binding of an iodinated substance P analog to an NK1 receptor on isolated cell membranes from rat anterior pituitary. Endocrinol. 124: 2548

    Article  CAS  Google Scholar 

  • Laurenzi, M.A., Persson, M.A.A., Dalsgaard, C.-J. and Haegerstrand, A., 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.

    Article  PubMed  CAS  Google Scholar 

  • Lechleiter, J., Hellmiss, R., Duerson, K., Ennulat, D., David, N., Clapham, D., and Peralta, E., 1990, Distinct sequence elements control the specificity of G protein activation by muscarinic acetylcholine receptor subtypes, EMBO J. 9: 4381.

    PubMed  CAS  Google Scholar 

  • Lemaire, I., 1988, Neurotensin enhances ILA production by activated alveolar macrophages, J. Immunol. 140: 2983.

    PubMed  CAS  Google Scholar 

  • Levine, J.D., Clark, R., Devor, M., Helms, C., Moskowitz, M.A., and Basbaum, A., 1984, Intraneuronal substance P contributes to the severity of experimental arthritis, Science 226: 547.

    Article  PubMed  CAS  Google Scholar 

  • Lieberman, A.P., Pitha, P.M., Shin, H.S., and Shin, M.L. 1989, Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus, Proc. Natl. Acad. Sci. USA 86: 6348.

    Article  PubMed  CAS  Google Scholar 

  • Lotz, M., Carson, D. and Vaughan, J.H., 1987, Substance P activation of rheumatoid synoviocytes: neural pathway in pathogenesis of arthritis, Science 238: 893.

    Article  Google Scholar 

  • Lotz, M., Vaughan, J.H., and Carson, D.A., 1988, Effect of neuropeptides on production of inflammatory cytokines by human monocytes, Science 241: 1218.

    Article  PubMed  CAS  Google Scholar 

  • Lundberg, J.M., Martling, C-R., Saria, A., Folkers, K., and Rosell, S, 1983, Cigarette smoke-induced airway edema due to activation of capsaicin-sensitive vagal afferents and substance P release, Neurosci. 10: 1361.

    Article  CAS  Google Scholar 

  • Mantyh, C.R., Gates, T.S., Zimmerman, R.P., Welton, M.L., Passaro, E.P., Vigna, S.R., Maggio, J.E., Kruger, L., and Mantyh, P.W., 1988, Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodes in surgical specimens obtained from patients with ulcerative colitis and Crohn disease, Proc. Natl. Acad. Sci. 85: 3235.

    Article  PubMed  CAS  Google Scholar 

  • Mantyh, P.W., Hunt, S.P., and Maggio, J.E., 1984, Substance P receptors: Localization by light microscopic autoradiography in rat brain using [3H]SP as the radio-ligand, Brain Res. 307: 147.

    Article  PubMed  CAS  Google Scholar 

  • Mantyh, P.W., Johnson, D.J., Boehmer, C.G., Calton, M.D., Vinters, H.V., Maggio, J.E., Too, H.-P. and Vigna, S.R., 1989, Substance P receptor binding sites are expressed by glia in vivo after neuronal injury, Proc. Natl. Acad. Sci. USA 86: 5193.

    Article  PubMed  CAS  Google Scholar 

  • Marshall, K.W., Chiu, B. and Inman, R.D., 1990, Substance P and arthritis: Analysis of plasma and synovial fluid levels, Arth. Rheum. 33: 87.

    Article  CAS  Google Scholar 

  • Martin, F.C., Anton, P.A., Gombein, J.A., Shanahan, F., and Merrill, J.E., Production of IL1 by microglia in response to substance P: role for a nonclassical NK1 receptor, J. Neuroimmunol.,in press, a.

    Google Scholar 

  • Martin, F.C., Charles, A.C., Sanderson, M.J., and Merrill, M.J., Substance P stimulates IL1 production by astrocytes via intracellular calcium, Brain Res. in press, b.

    Google Scholar 

  • Matthijs, B., Himpens, B., Peeters, T.L., and Vantrappen, G., 1990, Effects of substance P on [Ca2+]t and force in intact guinea pig ileal smooth muscle, Am. J. Physiol. 159: C150.

    Google Scholar 

  • Merrill, J.E., 1991, Effects of interleukin-1 and tumor necrosis factor-a on astrocytes, microglia, oligodendrocytes, and glial precursors in vitro, Devel. Neurosci. 13: 130.

    Article  CAS  Google Scholar 

  • McLean, S., Ganong, A.H., Seeger,. J.F., Bryce, D.K., Pratt, K.G., Reynolds, L.S., Siok, C.J., Lowe, J.A. III, and Heym, J., 1991, Activity and distribution of binding sites in brain of a non peptide substance P (NK) receptor antagonist, Science 251: 437.

    CAS  Google Scholar 

  • Moore, R.N., Osmand, A.P., Dunn, J.A., Joshi, J.G. and Rouse, B.T., 1988, Substance P augmentation of CSF-1-stimulated in vitro myelopoiesis, J. Immunology 141: 2699.

    CAS  Google Scholar 

  • Payan, D.G., Brewster, D.R., Missirian-Bastian, A. and Goetzel, E.J., 1984, Substance P recognition by a subset of human T lymphocytes, J. Clin. Invest. 74: 1532.

    Article  PubMed  CAS  Google Scholar 

  • Pearce, B., Murphy, S., Eds., 1983, “Neurotransmitter Receptors Coupled to Inositol Phospholipid Turnover and Ca2+ Flux: Consequences for Astrocyte Function,” Raven Press, Ltd., New York.

    Google Scholar 

  • Peck, R., 1987, Neuropeptides modulating macrophage function, Science 239: 264.

    Google Scholar 

  • Prpic, V., Weiel, J.E., Somers, S.D., DiGuiseppi, J., Gonias, S.L., Pizzo, S.V., Hamilton, T.A., Herman, B., and Adams, D.O., 1987, Effects of bacterial lipopolysaccharide on the hydrolysis of phosphatidylinositol-4,5-bisphosphate in murine peritoneal macrophages, J. Immunol. 139: 526.

    PubMed  CAS  Google Scholar 

  • Regoli, D., Drapeau, G., Dion, S. and D’Orleans-Juste, P., 1989, Receptors for substance P and related neurokinins, Pharmacology 38: 1.

    Article  PubMed  CAS  Google Scholar 

  • Ruff, M.R., Wahl, S.M., and Pert, C.B., 1985, Substance P receptor-mediated chemotaxis of human monocytes, Peptides 6 (Suppl 2): 107.

    Article  PubMed  CAS  Google Scholar 

  • Saito, K., Liu-Chen, L-Y., and Moskowitz, M.A., 1987, Substance P-like immunoreactivity in rat forebrain leptomeninges and cerebral vessels originates from the trigeminal but not sympathetic ganglia, Brain Res. 403: 55.

    Article  Google Scholar 

  • Sandberg, B.E.B., and Iversen, L.L., 1982, Substance P, J. Med. Chem. 25: 1009.

    Article  PubMed  CAS  Google Scholar 

  • Saria, A., 1984, Substance P in sensory nerve fibres contributes to the development of oedema in the rat hind paw after thermal injury, Brit. J. Pharmacol. 82: 217.

    Article  CAS  Google Scholar 

  • Schade, U.F., Burmeister, I., Elekes, E., Engel, R. and Wolter, D.T., 1989, Mononuclear phagocytes and eicosanoids: aspects of their synthesis and biological activities, Blut 59: 475.

    Article  PubMed  CAS  Google Scholar 

  • Shanahan, F., Denburg, J.A., Fox, J., Bienenstock, J., and Befus, D., 1985, Mast cell heterogeneity: effects of neuroenteric peptides on histamine release, J. Immunol. 135: 1331.

    PubMed  CAS  Google Scholar 

  • Shinomiya, H., and Nakano, M., 1987, Calcium ionophore A23187 does not stimulate lipopolysaccharide nonresponsive C3H/HeJ peritoneal macrophages to produce interleukin 1, J. Immunology 139: 2730.

    CAS  Google Scholar 

  • Snider, R.M., Constantine, J.W., III, J.A.L., Longo, K.P., Lebel, W.S., Woody, H.A., Drozda, S.E., Desai, M.C., Vinick, F.J., Spencer, R.W. and Hess, H.-J., 1991, A potent nonpeptide antagonist of the substance P (NK1) receptor, Science 251: 435.

    CAS  Google Scholar 

  • Stanisz, A.M., Bufus, D., and Bienenstock, J., 1986, Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferations by lymphocytes from Peyer’s patches, mesenteric lymph nodes, and spleen, J. Immunol. 136: 152.

    PubMed  CAS  Google Scholar 

  • Terada, Y., Shinomiya, H., and Nakano, M., 1989, Defect of calmodium-binding protein in expression of interleukin-113 gene by LPS-nonresponder C3H/HeJ mouse macrophages, Biochem. Biophys. Res. Com. 158: 723.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, K.L., Andrews, P.V., Khalil, Z., and Helme, R.D. 1989, Substance P induced hydrolysis of inositol phopolipids in rat skin in an in vivo model of inflammation, Neuropeptides 13: 191.

    Article  PubMed  CAS  Google Scholar 

  • Thureson-Klein, A., Hedqvist, P., Ohlen, A., Raud, J., and Lindbom, L., 1987, Leukotriene B4, platelet-activating factor and substance P as mediators of acute inflammation, Pathol. Immunopathol. Res. 6: 190.

    Article  PubMed  CAS  Google Scholar 

  • Tissot, M., Pradelles, P., and Giroud, J.P., 1988, Substance-P-like levels in inflammatory exudates. Inflammation 12: 25.

    Article  PubMed  CAS  Google Scholar 

  • Torrens, Y., Beaujouan, J.C., and Glowinski, J., 1985, Pharmacological characterization of two tachykinin binding sites in the rat cerebral cortex, Neuropeptides 6: 59.

    Article  PubMed  CAS  Google Scholar 

  • Torrens, Y., Beaujouan, J.C., Saffray, M., Daguet de MonTety, M.C., Bergstrom, L., and Glowinski, J., 1986, Substance P receptors in primary cultures of cortical astrocytes from the mouse, Proc. Natl. Acad. Sci. USA 83: 9216.

    Article  PubMed  CAS  Google Scholar 

  • Torrens, Y., Daguet De Montety, M.C., El Etr, M., Beaujouan, J.C., and Glowinski, J., 1989, Tachykinin receptors of the NK1 type (substance P) coupled positively to phospholipase Con cortical astrocytes from the newborn mouse in primary culture, J. Neurochem. 52: 1913.

    Article  PubMed  CAS  Google Scholar 

  • Wallengren, J., Ekman, R. and Moller, H., 1986, Substance P and vasoactive intestinal peptide in bullous and inflammatory skin disease, Acta Derm. Venereol. 66: 23.

    PubMed  CAS  Google Scholar 

  • Wienrich, M., and Kettenmanm, H., 1989, Activation of substance P receptors leads to membrane potential responses in cultured astrocytes, Glia 2: 155.

    Article  PubMed  CAS  Google Scholar 

  • Woodroofe, M.N., Sama, G.W., Wadhwa, M., Hayes, G.M., Loughlin, A.J., Tinker, A., and Cuzner, M.L., 1991, Detection of interleukin 1 and interleukin 6 in adult rat brain following mechanical injury by in vivo microdialysis: evidence of a role for microglia in cytokine production, J. Neuroimmunol. 33: 227.

    Article  PubMed  CAS  Google Scholar 

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Merrill, J.E., Charles, A.C., Martin, F.C. (1993). The Role of Substance P in Cytokine Production by Glial Cells. In: Fedoroff, S., Juurlink, B.H.J., Doucette, R. (eds) Biology and Pathology of Astrocyte-Neuron Interactions. Altschul Symposia Series, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9486-1_19

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