Research Article| Volume 162, ISSUE 2, P120-126, January 15, 1999

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DMSO induction of the leukotriene LTC4 by Lewis rat Schwann cells


      Schwann cells are capable of producing many immunomodulatory molecules, which indicates that they may play an active role in autoimmune diseases of the peripheral nervous system. We have previously reported production of the prostanoids prostaglandin E2 and thromboxane A2, products of arachidonic acid metabolism, by Schwann cells. This study reports that Schwann cells are capable of producing leukotriene C4, also a product of arachidonic acid metabolism. Production of leukotriene C4 was in response to pre-incubation of the Schwann cells with the cytokines interferon-γ and tumour necrosis factor-α followed by incubation with dimethylsulfoxide. The cytokines alone did not elicit a response nor did stimulation with calcium ionophore, phorbol ester or lipopolysaccharide.


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        • Angel J.
        • Berenbaum F.
        • Le Denmat C.
        • Nevalainen T.
        • Masliah J.
        • Fournier C.
        Interleukin-1-induced prostaglandin E2 biosynthesis in human synovial cells involves the activation of cytosolic phospholipase A2 and cyclooxygenase-2.
        Eur J Biochem. 1994; 226: 125-131
        • Argall K.G.
        • Armati P.J.
        • Pollard J.D.
        • Bonner J.G.
        Interactions between CD4+ T-cells and rat Schwann cells in vitro. 2. Cytotoxic effects of P2-specific CD4+ T-cell lines on Lewis rat Schwann cells.
        J Neuroimmunol. 1992; 40: 19-29
        • Argall K.G.
        • Armati P.J.
        • Pollard J.D.
        • Watson E.
        • Bonner J.G.
        Interactions between CD4+ T-cells and rat Schwann cells in vitro. 1. Antigen presentation by Lewis rat Schwann cells to P2-specific CD4+ T-cell lines.
        J Neuroimmunol. 1992; 40: 1-18
        • Armati P.J.
        • Karakotchian M.
        • Pollard J.D.
        • Constable A.L.
        The effect of exposure time to gamma interferon on MHC molecule expression in cultures of human dorsal root ganglia.
        Mol Cell Neurosci. 1990; 1: 49-57
        • Armati P.J.
        • Pollard J.D.
        • Gatenby P.A.
        Rat and human Schwann cells in vitro can synthesize and express MHC molecules.
        Muscle and Nerve. 1990; 113: 1106-1116
        • Beusenberg F.D.
        • Hoogsteden H.C.
        • Bonta I.L.
        • van Amsterdam J.G.
        Cyclic AMP enhancing drugs modulate eicosanoid release from human alveolar macrophages.
        Life Sciences. 1994; 54: 1269-1274
        • Bray M.A.
        Leukotrienes B4: an inflammatory mediator with vascular actions in vivo.
        Agents and Actions. 1982; 11: 51-61
        • Bray M.A.
        • Cunningham F.M.
        • Ford-Hutchinson A.W.
        • Smith M.J.
        Leukotriene B4: a mediator of vascular permeability.
        Brit J Pharmacol. 1981; 72: 483-486
        • Chan C.C.
        • Ford-Hutchinson A.
        Effects of synthetic leukotrienes on local blood flow and vascular permeability in porcine skin.
        J Invest Dermatol. 1985; 84: 154-157
        • Christman B.W.
        • Christman J.W.
        • Dworski R.
        • Blair I.A.
        • Prakash C.
        Prostaglandin E2 limits arachidonic acid availability and inhibits leukotriene B4 synthesis in rat alveolar macrophages by a nonphospholipase A2 mechanism.
        J Immunol. 1993; 151: 2096-2104
        • Constable A.L.
        • Armati P.J.
        • Toyka K.V.
        • Hartung H.-P.
        Production of the prostanoids, prostaglandin E2 and thromboxane B2 by rat Schwann cells in vitro.
        Brain Res. 1994; 635: 75-80
        • Dugas N.
        • Dugas B.
        • Kolb J.P.
        • Yamaoka K.
        • Delfraiss J.F.
        • Damais C.
        Role of leukotriene B4 in the interleukin-4-induced human mononuclear phagocyte activation.
        Immunol. 1996; 88: 384-388
        • Fels A.O.
        • Pawlowski N.A.
        • Cramer E.B.
        • King T.K.
        • Cohn Z.A.
        • Scott W.A.
        Human alveolar macrophages produce leukotriene N4.
        Proc Natl Acad Sci USA. 1982; 79: 7866-7870
        • Feng L.
        • Xia Y.
        • Garcia G.E.
        • Hwang D.
        • Wilson C.B.
        Involvement of reactive oxygen intermediates in cyclooxygenase-2 expression induced by interleukin-1, tumor necrosis factor-alpha, and lipopolysaccharide.
        J Clin Invest. 1995; 95: 1669-1675
        • Ford-Hutchinson A.W.
        • Bray M.A.
        • Doig M.V.
        • Shipley M.E.
        • Smith M.J.
        Leukotriene B. A potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes.
        Nature. 1980; 286: 264-265
        • Ford A.
        • Britton W.J.
        • Armati P.J.
        Schwann cells are able to present exogenous Mycobacterial hsp70 to antigen specific T lymphocytes.
        J Neuroimmunol. 1993; 42: 151-160
        • Gold R.
        • Toyka K.V.
        • Hartung H.P.
        Synergistic effect of IFN-gamma and TNF-alpha on expression of immune molecules and antigen presentation by Schwann cells.
        Cell Immunol. 1995; 165: 65-70
        • Gold R.
        • Zielasek J.
        • Kiefer R.
        • Toyka K.V.
        • Hartung H.P.
        Secretion of nitrite by Schwann cells and its effect on T-cell activation in vitro.
        Cell Immunol. 1996; 168: 69-77
        • Goldman G.
        • Welbourn R.
        • Kobzik L.
        • Valeri C.R.
        • Shepro D.
        • Hechtman H.B.
        Synergism between leukotriene B4 and thromboxane A2 in mediating acid-aspiration injury.
        Surgery. 1992; 111: 55-61
        • Goldyne M.E.
        • Burrish G.F.
        • Poubelle P.
        • Borgeat P.
        Arachidonic acid metabolism among human mononuclear leukocytes.
        Lipoxygenase-related pathways. J Biol Chem. 1984; 259: 8815-8819
        • Goldyne M.E.
        • Rea L.
        Stimulated T cell and natural killer (NK) cell lines fail to synthesize leukotriene B4.
        Prostaglandins. 1987; 34: 783-795
        • Hartung H.-P.
        • Toyka K.
        Leukotriene production by cultured astroglial cells.
        Brain Res. 1987; 435: 367-370
        • Hartung H.-P.
        • Toyka K.V.
        Phorbol diester TPA elicits prostaglandin E release from cultured rat astrocytes.
        Brain Res. 1987; 417: 347-349
        • Hartung H.-P.
        • Toyka K.V.
        Primary rat astroglial cultures can generate leukotriene B4.
        J Neuroimmunol. 1988; 19: 237-243
        • Hartung H.P.
        • Schafer B.
        • Heininger K.
        • Toyka K.V.
        Suppression of experimental autoimmune neuritis by the oxygen radical scavengers superoxide dismutase and catalase.
        Ann Neurol. 1988; 23: 453-460
        • Hatzelmann A.
        • Schatz M.
        • Ullrich V.
        Involvement of glutathione peroxidase activity in the stimulation of 5-lipoxygenase activity by glutathione-depleting agents in human polymorphonuclear leukocytes.
        Eur J Biochem. 1989; 180: 527-533
        • Holtzman M.J.
        • Aizawa H.
        • Nadel J.A.
        • Goetzl E.J.
        Selective generation of leukotriene B4 by tracheal epithelial cells from dogs.
        Biochem Biophys Res Comm. 1983; 114: 1071-1076
        • Ishii Y.
        • Lo S.K.
        • Malik A.B.
        Neutrophil adhesion to TNF alpha-activated endothelial cells potentiates leukotriene B4 production.
        J Cell Physiol. 1992; 153: 187-195
        • Jakobsson P.J.
        • Odlander B.
        • Steinhilber D.
        • Rosen A.
        • Claesson H.E.
        Human B lymphocytes possess 5-lipoxygenase activity and convert arachidonic acid to leukotriene B4.
        Biochem Biophys Res Comm. 1991; 178: 302-308
        • Kanwar S.
        • Johnston B.
        • Kubes P.
        Leukotriene C4/D4 induces P-selectin and sialyl Lewisx-dependent alterations in leukocyte kinetics in vivo.
        Circul Res. 1995; 77: 879-887
        • Krump E.
        • Pouliot M.
        • Naccache P.H.
        • Borgeat P.
        Leukotriene synthesis in calcium-depleted human neurotphils: arachidonic acid release correlates with calcuim influx.
        Biochem J. 1995; 310: 681-688
        • Lewis R.A.
        • Austen K.F.
        • Soberman R.J.
        Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. (Review) (136 refs.).
        N Eng J Med. 1990; 323: 645-655
        • Lilje O.
        • Armati P.J.
        An improved protocol for immunogold staining for scanning electron microscopy of cultured cells.
        J Neurosci Meth. 1995; 58: 77-80
        • Lilje O.
        • Armati P.J.
        The distribution and abundance of MHC and ICAM-1 on Schwann cells in vitro.
        J Neuroimmunol. 1997; 77: 75-84
        • Martin T.R.
        • Altman L.C.
        • Albert R.K.
        • Henderson W.R.
        Leukotriene B4 production by the human alveolar macrophage: a potential mechanism for amplifying inflammation in the lung.
        Am Rev Resp Dis. 1984; 129: 106-111
        • Morley P.
        • Whitfield J.F.
        The differentiation inducer, dimethyl sulfoxide, transiently increases the intracellular calcium ion concentration in various cell types.
        J Cell Physiol. 1993; 156: 219-225
      1. Movat HZ, Rett., Burrowes CE, Johnston MG, The in vivo effect of leukotriene B4 on polymorphonuclear leukocytes and the microcirculation. Comparison with activated complement (C5a des Arg) and enhancement by prostaglandin E2. Am J Pathol 1984;115:233–44.

        • Murwani R.
        • Hodgkinson S.
        • Armati P.J.
        The production of cytokines by Lewis rat Schwann cells.
        J Neuroimmunol. 1996; 71: 65-71
        • Neu I.
        • Mallinger J.
        • Wildfeuer A.
        • Mehlber L.
        Leukotrienes in the cerebrospinal fluid of multiple sclerosis patients.
        Acta Neurol Scand. 1992; 86: 586-587
        • Ouwendijk R.J.
        • Zijlstra F.J.
        • van den Broek A.M.
        • Brouwer A.
        • Wilson J.H.
        • Vincent J.E.
        Comparison of the production of eicosanoids by human and rat peritoneal macrophages and rat Kupffer cells.
        Prostaglandins. 1988; 35: 437-446
        • Payan D.G.
        • Goetzl E.J.
        The dependence of human T-lymphocyte migration on the 5-lipoxygenation of endogenous arachidonic acid.
        J Clin Immunol. 1981; 1: 266-271
        • Payan D.G.
        • Missirian-Bastian A.
        • Goetzl E.J.
        Human T-lymphocyte subset specificity of the regulatory effects of leukotriene B4.
        Proc Natl Acad Sci USA. 1984; 81: 3501-3505
        • Rankin J.A.
        • Schrader C.E.
        • Smith S.M.
        • Lewis R.A.
        Recombinant interon-gamma primes alveolar macrophages cultured in vitro for the release of leukotriene B4 in response to IgG stimulation.
        J Clin Invest. 1989; 83: 1691-1700
        • Rzigalinski B.A.
        • Rosenthal M.D.
        Effects of DMSO-induced differentiation on arachidonate mobilization in the human histiocytic lymphoma cell line U937: responsiveness to sub-micromolar calcium ionophore A23187 and phorbol esters.
        Biochim et Biophys Acta. 1994; 1223: 219-225
        • Schatz-Munding M.
        • Hatzelmann A.
        • Ullrich V.
        The involvement of extracellular calcium in the formation of 5-lipoxygenase metabolites by human polymorphonuclear leukocytes.
        Eur J Biochem. 1991; 197: 487-493
        • Scher W.
        • Waxman S.
        Effects of dexamethasone and phorbol myristate acetate on the induction of differentiation in mouse erythroleukemic cells by dimethyl sulfoxide, proteases, and other compounds.
        Ann NY Acad Sci. 1983; 411: 180-190
        • Skundric D.S.
        • Bealmar B.
        • Lisak R.P.
        Induced upregulation of IL-1, IL-1RA and ILR type I gene expression by Schwann cells.
        J Neuroimmunol. 1997; 74: 9-18
        • Spies J.
        • Bonner J.G.
        • Westland K.W.
        • Pollard J.D.
        Blood nerve barrier breakdown by activated P2 specific T cells.
        Brain. 1995; 118: 857-868
        • Surette M.E.
        • Nadeau M.
        • Borgeat P.
        • Gosselin J.
        Priming of human peripheral blood mononuclear cells with lipopolysaccharides for enhanced arachidonic acid release and leukotriene synthesis.
        J Leuk Biol. 1996; 59: 709-715
        • Tsai C.P.
        • Pollard J.D.
        • Armati P.J.
        Interferon-gamma inhibition suppresses experimental allergic neuritis: modulation of major histocompatibility complex expression of Schwann cells in vitro.
        J Neuroimmunol. 1991; 31: 133-145
        • Vance D.E.
        Metabolism of glycerolipids, sphingolipids and prostaglandins.
        in: Zubay G. Biochemistry. Addison-Wesley Publishing Company, Reading, Massachusets1986: 505-542
        • Wekerle H.
        • Schwab M.
        • Linington C.
        • Myermann R.
        Antigen presentation in the peripheral nervous system: Schwann cells present endogenous myelin autoantigens to lymphocytes.
        Eur J Immunol. 1986; 16: 1551-1557
        • Withnall M.T.
        • Pennington A.
        • Wiseman D.
        Characterisation of cytosolic phospholipase A2 as mediator of the enhanced arachidonic acid release from dimethyl sulphoxide differentiated I937 cells.
        Biochem Pharmacol. 1995; 50: 1893-1902
        • Wong G.W.H.
        • Bartlett P.F.
        • Clark-Lewis I.
        • McKim-Breschkin J.L.
        • Schrader J.W.
        Interferon-gamma induces the expression of H-2 and Ia antigens on brain cells.
        J Neuroimmunol. 1985; 7: 255-278