Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Apr;65(4):1223–1227. doi: 10.1128/iai.65.4.1223-1227.1997

Intervention in endotoxin shock by sulfatide (I3SO3-GalCer) with a concomitant reduction in tumor necrosis factor alpha production.

H Higashi 1, Y Suzuki 1, N Mukaida 1, N Takahashi 1, D Miyamoto 1, K Matsushima 1
PMCID: PMC175121  PMID: 9119455

Abstract

Accumulating evidence indicates that tumor necrosis factor alpha (TNF-alpha) is a principal mediator of endotoxin shock. We previously reported that the action as well as the production of TNF requires the adhesion of leukocytes to the endothelium through integrin beta2 and intercellular adhesion molecule 1. In order to elucidate the roles of the initial interaction of the leukocytes with the endothelium through the selectins, we have examined the effects of a ligand for L- and P-selectins, sulfatide, on endotoxin shock in mice. Consistent with previous reports, a single injection of a high dose of endotoxin caused acute lethality, marked hypotension, leukopenia, and elevation in serum TNF-alpha levels. Pretreatment with sulfatide prevented acute lethality and hypotension, but not leukopenia, with a concomitant reduction in the increase in serum TNF-alpha levels. Moreover, pretreatment with sulfatide inhibited lipopolysaccharide (LPS)-induced TNF-alpha production by a human monocytic cell line, THP-1, in a dose-dependent manner. These results suggest either that selectin is critically involved in conferring the responsiveness of leukocytes to LPS or that sulfatide interferes with the intracellular signaling pathway which leads to TNF-alpha gene activation.

Full Text

The Full Text of this article is available as a PDF (156.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arbonés M. L., Ord D. C., Ley K., Ratech H., Maynard-Curry C., Otten G., Capon D. J., Tedder T. F. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity. 1994 Jul;1(4):247–260. doi: 10.1016/1074-7613(94)90076-0. [DOI] [PubMed] [Google Scholar]
  2. Aruffo A., Kolanus W., Walz G., Fredman P., Seed B. CD62/P-selectin recognition of myeloid and tumor cell sulfatides. Cell. 1991 Oct 4;67(1):35–44. doi: 10.1016/0092-8674(91)90570-o. [DOI] [PubMed] [Google Scholar]
  3. Baeuerle P. A., Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 1994;12:141–179. doi: 10.1146/annurev.iy.12.040194.001041. [DOI] [PubMed] [Google Scholar]
  4. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  5. Bhat S., Mettus R. V., Reddy E. P., Ugen K. E., Srikanthan V., Williams W. V., Weiner D. B. The galactosyl ceramide/sulfatide receptor binding region of HIV-1 gp120 maps to amino acids 206-275. AIDS Res Hum Retroviruses. 1993 Feb;9(2):175–181. doi: 10.1089/aid.1993.9.175. [DOI] [PubMed] [Google Scholar]
  6. Celi A., Pellegrini G., Lorenzet R., De Blasi A., Ready N., Furie B. C., Furie B. P-selectin induces the expression of tissue factor on monocytes. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8767–8771. doi: 10.1073/pnas.91.19.8767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Constantin G., Laudanna C., Baron P., Berton G. Sulfatides trigger cytokine gene expression and secretion in human monocytes. FEBS Lett. 1994 Aug 15;350(1):66–70. doi: 10.1016/0014-5793(94)00735-7. [DOI] [PubMed] [Google Scholar]
  8. Diacovo T. G., Roth S. J., Buccola J. M., Bainton D. F., Springer T. A. Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18. Blood. 1996 Jul 1;88(1):146–157. [PubMed] [Google Scholar]
  9. Ding A. H., Nathan C. F., Stuehr D. J. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988 Oct 1;141(7):2407–2412. [PubMed] [Google Scholar]
  10. Fan S. T., Edgington T. S. Integrin regulation of leukocyte inflammatory functions. CD11b/CD18 enhancement of the tumor necrosis factor-alpha responses of monocytes. J Immunol. 1993 Apr 1;150(7):2972–2980. [PubMed] [Google Scholar]
  11. Fujioka N., Mukaida N., Harada A., Akiyama M., Kasahara T., Kuno K., Ooi A., Mai M., Matsushima K. Preparation of specific antibodies against murine IL-1ra and the establishment of IL-1ra as an endogenous regulator of bacteria-induced fulminant hepatitis in mice. J Leukoc Biol. 1995 Jul;58(1):90–98. doi: 10.1002/jlb.58.1.90. [DOI] [PubMed] [Google Scholar]
  12. Harada A., Sekido N., Kuno K., Akiyama M., Kasahara T., Nakanishi I., Mukaida N., Matsushima K. Expression of recombinant rabbit IL-8 in Escherichia coli and establishment of the essential involvement of IL-8 in recruiting neutrophils into lipopolysaccharide-induced inflammatory site of rabbit skin. Int Immunol. 1993 Jun;5(6):681–690. doi: 10.1093/intimm/5.6.681. [DOI] [PubMed] [Google Scholar]
  13. Holt G. D., Krivan H. C., Gasic G. J., Ginsburg V. Antistasin, an inhibitor of coagulation and metastasis, binds to sulfatide (Gal(3-SO4) beta 1-1Cer) and has a sequence homology with other proteins that bind sulfated glycoconjugates. J Biol Chem. 1989 Jul 25;264(21):12138–12140. [PubMed] [Google Scholar]
  14. Holt G. D., Pangburn M. K., Ginsburg V. Properdin binds to sulfatide [Gal(3-SO4)beta 1-1 Cer] and has a sequence homology with other proteins that bind sulfated glycoconjugates. J Biol Chem. 1990 Feb 15;265(5):2852–2855. [PubMed] [Google Scholar]
  15. Hwang S. T., Singer M. S., Giblin P. A., Yednock T. A., Bacon K. B., Simon S. I., Rosen S. D. GlyCAM-1, a physiologic ligand for L-selectin, activates beta 2 integrins on naive peripheral lymphocytes. J Exp Med. 1996 Oct 1;184(4):1343–1348. doi: 10.1084/jem.184.4.1343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ikeda N., Mukaida N., Kaneko S., Fujioka N., Su S., Nariuchi H., Unoura M., Harada K., Nakanuma Y., Kobayashi K. Prevention of endotoxin-induced acute lethality in Propionibacterium acnes-primed rabbits by an antibody to leukocyte integrin beta 2 with concomitant reduction of cytokine production. Infect Immun. 1995 Dec;63(12):4812–4817. doi: 10.1128/iai.63.12.4812-4817.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Imai Y., True D. D., Singer M. S., Rosen S. D. Direct demonstration of the lectin activity of gp90MEL, a lymphocyte homing receptor. J Cell Biol. 1990 Sep;111(3):1225–1232. doi: 10.1083/jcb.111.3.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Johnson R. C., Mayadas T. N., Frenette P. S., Mebius R. E., Subramaniam M., Lacasce A., Hynes R. O., Wagner D. D. Blood cell dynamics in P-selectin-deficient mice. Blood. 1995 Aug 1;86(3):1106–1114. [PubMed] [Google Scholar]
  19. Kajihara J., Guoji Y., Kato K., Suzuki Y. Sulfatide, a specific sugar ligand for L-selectin, blocks CCl4-induced liver inflammation in rats. Biosci Biotechnol Biochem. 1995 Jan;59(1):155–157. doi: 10.1271/bbb.59.155. [DOI] [PubMed] [Google Scholar]
  20. Kilbourn R. G., Griffith O. W. Inhibition of inducible nitric oxide synthase with inhibitors of tetrahydrobiopterin biosynthesis. J Natl Cancer Inst. 1992 Nov 4;84(21):1672–1672. doi: 10.1093/jnci/84.21.1672. [DOI] [PubMed] [Google Scholar]
  21. Kilbourn R. G., Gross S. S., Jubran A., Adams J., Griffith O. W., Levi R., Lodato R. F. NG-methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide. Proc Natl Acad Sci U S A. 1990 May;87(9):3629–3632. doi: 10.1073/pnas.87.9.3629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Laudanna C., Constantin G., Baron P., Scarpini E., Scarlato G., Cabrini G., Dechecchi C., Rossi F., Cassatella M. A., Berton G. Sulfatides trigger increase of cytosolic free calcium and enhanced expression of tumor necrosis factor-alpha and interleukin-8 mRNA in human neutrophils. Evidence for a role of L-selectin as a signaling molecule. J Biol Chem. 1994 Feb 11;269(6):4021–4026. [PubMed] [Google Scholar]
  23. Ley K., Bullard D. C., Arbonés M. L., Bosse R., Vestweber D., Tedder T. F., Beaudet A. L. Sequential contribution of L- and P-selectin to leukocyte rolling in vivo. J Exp Med. 1995 Feb 1;181(2):669–675. doi: 10.1084/jem.181.2.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ley K., Tedder T. F. Leukocyte interactions with vascular endothelium. New insights into selectin-mediated attachment and rolling. J Immunol. 1995 Jul 15;155(2):525–528. [PubMed] [Google Scholar]
  25. Mayadas T. N., Johnson R. C., Rayburn H., Hynes R. O., Wagner D. D. Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell. 1993 Aug 13;74(3):541–554. doi: 10.1016/0092-8674(93)80055-j. [DOI] [PubMed] [Google Scholar]
  26. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  27. Mulligan M. S., Miyasaka M., Suzuki Y., Kawashima H., Iizuka M., Hasegawa A., Kiso M., Warner R. L., Ward P. A., Suzuki T. Anti-inflammatory effects of sulfatides in selectin-dependent acute lung injury. Int Immunol. 1995 Jul;7(7):1107–1113. doi: 10.1093/intimm/7.7.1107. [DOI] [PubMed] [Google Scholar]
  28. Natanson C., Fink M. P., Ballantyne H. K., MacVittie T. J., Conklin J. J., Parrillo J. E. Gram-negative bacteremia produces both severe systolic and diastolic cardiac dysfunction in a canine model that simulates human septic shock. J Clin Invest. 1986 Jul;78(1):259–270. doi: 10.1172/JCI112559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nava E., Palmer R. M., Moncada S. Inhibition of nitric oxide synthesis in septic shock: how much is beneficial? Lancet. 1991 Dec 21;338(8782-8783):1555–1557. doi: 10.1016/0140-6736(91)92375-c. [DOI] [PubMed] [Google Scholar]
  30. Petros A., Bennett D., Vallance P. Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet. 1991 Dec 21;338(8782-8783):1557–1558. doi: 10.1016/0140-6736(91)92376-d. [DOI] [PubMed] [Google Scholar]
  31. Petros A., Lamb G., Leone A., Moncada S., Bennett D., Vallance P. Effects of a nitric oxide synthase inhibitor in humans with septic shock. Cardiovasc Res. 1994 Jan;28(1):34–39. doi: 10.1093/cvr/28.1.34. [DOI] [PubMed] [Google Scholar]
  32. Pfeffer K., Matsuyama T., Kündig T. M., Wakeham A., Kishihara K., Shahinian A., Wiegmann K., Ohashi P. S., Krönke M., Mak T. W. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell. 1993 May 7;73(3):457–467. doi: 10.1016/0092-8674(93)90134-c. [DOI] [PubMed] [Google Scholar]
  33. Roberts D. D., Haverstick D. M., Dixit V. M., Frazier W. A., Santoro S. A., Ginsburg V. The platelet glycoprotein thrombospondin binds specifically to sulfated glycolipids. J Biol Chem. 1985 Aug 5;260(16):9405–9411. [PubMed] [Google Scholar]
  34. Roberts D. D., Rao C. N., Magnani J. L., Spitalnik S. L., Liotta L. A., Ginsburg V. Laminin binds specifically to sulfated glycolipids. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1306–1310. doi: 10.1073/pnas.82.5.1306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Roberts D. D., Williams S. B., Gralnick H. R., Ginsburg V. von Willebrand factor binds specifically to sulfated glycolipids. J Biol Chem. 1986 Mar 5;261(7):3306–3309. [PubMed] [Google Scholar]
  36. Rothe J., Lesslauer W., Lötscher H., Lang Y., Koebel P., Köntgen F., Althage A., Zinkernagel R., Steinmetz M., Bluethmann H. Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature. 1993 Aug 26;364(6440):798–802. doi: 10.1038/364798a0. [DOI] [PubMed] [Google Scholar]
  37. Subramaniam M., Saffaripour S., Watson S. R., Mayadas T. N., Hynes R. O., Wagner D. D. Reduced recruitment of inflammatory cells in a contact hypersensitivity response in P-selectin-deficient mice. J Exp Med. 1995 Jun 1;181(6):2277–2282. doi: 10.1084/jem.181.6.2277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Suzuki Y., Toda Y., Tamatani T., Watanabe T., Suzuki T., Nakao T., Murase K., Kiso M., Hasegawa A., Tadano-Aritomi K. Sulfated glycolipids are ligands for a lymphocyte homing receptor, L-selectin (LECAM-1), Binding epitope in sulfated sugar chain. Biochem Biophys Res Commun. 1993 Jan 29;190(2):426–434. doi: 10.1006/bbrc.1993.1065. [DOI] [PubMed] [Google Scholar]
  39. Tedder T. F., Steeber D. A., Chen A., Engel P. The selectins: vascular adhesion molecules. FASEB J. 1995 Jul;9(10):866–873. [PubMed] [Google Scholar]
  40. Tedder T. F., Steeber D. A., Pizcueta P. L-selectin-deficient mice have impaired leukocyte recruitment into inflammatory sites. J Exp Med. 1995 Jun 1;181(6):2259–2264. doi: 10.1084/jem.181.6.2259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Thiemermann C., Vane J. Inhibition of nitric oxide synthesis reduces the hypotension induced by bacterial lipopolysaccharides in the rat in vivo. Eur J Pharmacol. 1990 Jul 17;182(3):591–595. doi: 10.1016/0014-2999(90)90062-b. [DOI] [PubMed] [Google Scholar]
  42. Tracey K. J., Beutler B., Lowry S. F., Merryweather J., Wolpe S., Milsark I. W., Hariri R. J., Fahey T. J., 3rd, Zentella A., Albert J. D. Shock and tissue injury induced by recombinant human cachectin. Science. 1986 Oct 24;234(4775):470–474. doi: 10.1126/science.3764421. [DOI] [PubMed] [Google Scholar]
  43. Tracey K. J., Fong Y., Hesse D. G., Manogue K. R., Lee A. T., Kuo G. C., Lowry S. F., Cerami A. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature. 1987 Dec 17;330(6149):662–664. doi: 10.1038/330662a0. [DOI] [PubMed] [Google Scholar]
  44. Varki A. Selectin ligands. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7390–7397. doi: 10.1073/pnas.91.16.7390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Waddell T. K., Fialkow L., Chan C. K., Kishimoto T. K., Downey G. P. Potentiation of the oxidative burst of human neutrophils. A signaling role for L-selectin. J Biol Chem. 1994 Jul 15;269(28):18485–18491. [PubMed] [Google Scholar]
  46. Waddell T. K., Fialkow L., Chan C. K., Kishimoto T. K., Downey G. P. Signaling functions of L-selectin. Enhancement of tyrosine phosphorylation and activation of MAP kinase. J Biol Chem. 1995 Jun 23;270(25):15403–15411. doi: 10.1074/jbc.270.25.15403. [DOI] [PubMed] [Google Scholar]
  47. Watanabe S., Mukaida N., Ikeda N., Akiyama M., Harada A., Nakanishi I., Nariuchi H., Watanabe Y., Matsushima K. Prevention of endotoxin shock by an antibody against leukocyte integrin beta 2 through inhibiting production and action of TNF. Int Immunol. 1995 Jul;7(7):1037–1046. doi: 10.1093/intimm/7.7.1037. [DOI] [PubMed] [Google Scholar]
  48. Weyrich A. S., McIntyre T. M., McEver R. P., Prescott S. M., Zimmerman G. A. Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion. Signal integration and NF-kappa B translocation. J Clin Invest. 1995 May;95(5):2297–2303. doi: 10.1172/JCI117921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Xu H., Gonzalo J. A., St Pierre Y., Williams I. R., Kupper T. S., Cotran R. S., Springer T. A., Gutierrez-Ramos J. C. Leukocytosis and resistance to septic shock in intercellular adhesion molecule 1-deficient mice. J Exp Med. 1994 Jul 1;180(1):95–109. doi: 10.1084/jem.180.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Zhang X., Morrison D. C. Lipopolysaccharide-induced selective priming effects on tumor necrosis factor alpha and nitric oxide production in mouse peritoneal macrophages. J Exp Med. 1993 Feb 1;177(2):511–516. doi: 10.1084/jem.177.2.511. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES