Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Jan;65(1):89–94. doi: 10.1128/iai.65.1.89-94.1997

Induction of tumor necrosis factor production from monocytes stimulated with mannuronic acid polymers and involvement of lipopolysaccharide-binding protein, CD14, and bactericidal/permeability-increasing factor.

T G Jahr 1, L Ryan 1, A Sundan 1, H S Lichenstein 1, G Skjåk-Braek 1, T Espevik 1
PMCID: PMC174560  PMID: 8975896

Abstract

Well-defined polysaccharides, such as beta1-4-linked D-mannuronic acid (poly[M]) derived from Pseudomonas aeruginosa, induce monocytes to produce tumor necrosis factor (TNF) through a pathway involving membrane CD14. In this study we have investigated the effects of soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP), and bactericidal/permeability-increasing factor (BPI) on poly(M) binding to monocytes and induction of TNF production. We show that LBP increased the TNF production from monocytes stimulated with poly(M). Addition of sCD14 alone had only minor effects, but when it was added together with LBP, a rise in TNF production was seen. BPI was found to inhibit TNF production from monocytes stimulated with poly(M) in the presence of LBP, LBP-sCD14, or 10% human serum. Binding studies showed that poly(M) bound to LBP- and BPI-coated immunowells, while no significant binding of poly(M) to sCD14-coated wells in the absence of serum was observed. Binding of poly(M) to monocytes was also examined by flow cytometry, and it was shown that the addition of LBP or 10% human serum clearly increased the binding of poly(M) to monocytes. BPI inhibited the binding of poly(M) to monocytes in the presence of LBP, LBP-sCD14, or 10% human serum. Our data demonstrate a role for LBP, LBP-sCD14, and BPI in modulating TNF responses of defined polysaccharides.

Full Text

The Full Text of this article is available as a PDF (218.0 KB).

Selected References

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

  1. Bøyum A. Isolation of lymphocytes, granulocytes and macrophages. Scand J Immunol. 1976 Jun;Suppl 5:9–15. [PubMed] [Google Scholar]
  2. Dentener M. A., Von Asmuth E. J., Francot G. J., Marra M. N., Buurman W. A. Antagonistic effects of lipopolysaccharide binding protein and bactericidal/permeability-increasing protein on lipopolysaccharide-induced cytokine release by mononuclear phagocytes. Competition for binding to lipopolysaccharide. J Immunol. 1993 Oct 15;151(8):4258–4265. [PubMed] [Google Scholar]
  3. Espevik T., Nissen-Meyer J. A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes. J Immunol Methods. 1986 Dec 4;95(1):99–105. doi: 10.1016/0022-1759(86)90322-4. [DOI] [PubMed] [Google Scholar]
  4. Espevik T., Otterlei M., Skjåk-Braek G., Ryan L., Wright S. D., Sundan A. The involvement of CD14 in stimulation of cytokine production by uronic acid polymers. Eur J Immunol. 1993 Jan;23(1):255–261. doi: 10.1002/eji.1830230140. [DOI] [PubMed] [Google Scholar]
  5. Frey E. A., Miller D. S., Jahr T. G., Sundan A., Bazil V., Espevik T., Finlay B. B., Wright S. D. Soluble CD14 participates in the response of cells to lipopolysaccharide. J Exp Med. 1992 Dec 1;176(6):1665–1671. doi: 10.1084/jem.176.6.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gazzano-Santoro H., Parent J. B., Grinna L., Horwitz A., Parsons T., Theofan G., Elsbach P., Weiss J., Conlon P. J. High-affinity binding of the bactericidal/permeability-increasing protein and a recombinant amino-terminal fragment to the lipid A region of lipopolysaccharide. Infect Immun. 1992 Nov;60(11):4754–4761. doi: 10.1128/iai.60.11.4754-4761.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hailman E., Lichenstein H. S., Wurfel M. M., Miller D. S., Johnson D. A., Kelley M., Busse L. A., Zukowski M. M., Wright S. D. Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J Exp Med. 1994 Jan 1;179(1):269–277. doi: 10.1084/jem.179.1.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Haziot A., Rong G. W., Bazil V., Silver J., Goyert S. M. Recombinant soluble CD14 inhibits LPS-induced tumor necrosis factor-alpha production by cells in whole blood. J Immunol. 1994 Jun 15;152(12):5868–5876. [PubMed] [Google Scholar]
  9. Heumann D., Gallay P., Betz-Corradin S., Barras C., Baumgartner J. D., Glauser M. P. Competition between bactericidal/permeability-increasing protein and lipopolysaccharide-binding protein for lipopolysaccharide binding to monocytes. J Infect Dis. 1993 Jun;167(6):1351–1357. doi: 10.1093/infdis/167.6.1351. [DOI] [PubMed] [Google Scholar]
  10. Ingalls R. R., Golenbock D. T. CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide. J Exp Med. 1995 Apr 1;181(4):1473–1479. doi: 10.1084/jem.181.4.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jahr T. G., Sundan A., Lichenstein H. S., Espevik T. Influence of CD14, LBP and BPI in the monocyte response to LPS of different polysaccharide chain length. Scand J Immunol. 1995 Jul;42(1):119–127. doi: 10.1111/j.1365-3083.1995.tb03634.x. [DOI] [PubMed] [Google Scholar]
  12. Kulseng B., Skjåk-Braek G., Følling I., Espevik T. TNF production from peripheral blood mononuclear cells in diabetic patients after stimulation with alginate and lipopolysaccharide. Scand J Immunol. 1996 Mar;43(3):335–340. doi: 10.1046/j.1365-3083.1996.d01-43.x. [DOI] [PubMed] [Google Scholar]
  13. Kusunoki T., Hailman E., Juan T. S., Lichenstein H. S., Wright S. D. Molecules from Staphylococcus aureus that bind CD14 and stimulate innate immune responses. J Exp Med. 1995 Dec 1;182(6):1673–1682. doi: 10.1084/jem.182.6.1673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Labeta M. O., Durieux J. J., Fernandez N., Herrmann R., Ferrara P. Release from a human monocyte-like cell line of two different soluble forms of the lipopolysaccharide receptor, CD14. Eur J Immunol. 1993 Sep;23(9):2144–2151. doi: 10.1002/eji.1830230915. [DOI] [PubMed] [Google Scholar]
  15. Liabakk N. B., Nustad K., Espevik T. A rapid and sensitive immunoassay for tumor necrosis factor using magnetic monodisperse polymer particles. J Immunol Methods. 1990 Dec 5;134(2):253–259. doi: 10.1016/0022-1759(90)90387-b. [DOI] [PubMed] [Google Scholar]
  16. Marra M. N., Wilde C. G., Griffith J. E., Snable J. L., Scott R. W. Bactericidal/permeability-increasing protein has endotoxin-neutralizing activity. J Immunol. 1990 Jan 15;144(2):662–666. [PubMed] [Google Scholar]
  17. Mathison J. C., Tobias P. S., Wolfson E., Ulevitch R. J. Plasma lipopolysaccharide (LPS)-binding protein. A key component in macrophage recognition of gram-negative LPS. J Immunol. 1992 Jul 1;149(1):200–206. [PubMed] [Google Scholar]
  18. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  19. Nockher W. A., Bergmann L., Scherberich J. E. Increased soluble CD14 serum levels and altered CD14 expression of peripheral blood monocytes in HIV-infected patients. Clin Exp Immunol. 1994 Dec;98(3):369–374. doi: 10.1111/j.1365-2249.1994.tb05499.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Otterlei M., Ostgaard K., Skjåk-Braek G., Smidsrød O., Soon-Shiong P., Espevik T. Induction of cytokine production from human monocytes stimulated with alginate. J Immunother (1991) 1991 Aug;10(4):286–291. doi: 10.1097/00002371-199108000-00007. [DOI] [PubMed] [Google Scholar]
  21. Otterlei M., Sundan A., Skjåk-Braek G., Ryan L., Smidsrød O., Espevik T. Similar mechanisms of action of defined polysaccharides and lipopolysaccharides: characterization of binding and tumor necrosis factor alpha induction. Infect Immun. 1993 May;61(5):1917–1925. doi: 10.1128/iai.61.5.1917-1925.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Otterlei M., Vårum K. M., Ryan L., Espevik T. Characterization of binding and TNF-alpha-inducing ability of chitosans on monocytes: the involvement of CD14. Vaccine. 1994 Jul;12(9):825–832. doi: 10.1016/0264-410x(94)90292-5. [DOI] [PubMed] [Google Scholar]
  23. Pier G. B., Matthews W. J., Jr, Eardley D. D. Immunochemical characterization of the mucoid exopolysaccharide of Pseudomonas aeruginosa. J Infect Dis. 1983 Mar;147(3):494–503. doi: 10.1093/infdis/147.3.494. [DOI] [PubMed] [Google Scholar]
  24. Pugin J., Heumann I. D., Tomasz A., Kravchenko V. V., Akamatsu Y., Nishijima M., Glauser M. P., Tobias P. S., Ulevitch R. J. CD14 is a pattern recognition receptor. Immunity. 1994 Sep;1(6):509–516. doi: 10.1016/1074-7613(94)90093-0. [DOI] [PubMed] [Google Scholar]
  25. Pugin J., Schürer-Maly C. C., Leturcq D., Moriarty A., Ulevitch R. J., Tobias P. S. Lipopolysaccharide activation of human endothelial and epithelial cells is mediated by lipopolysaccharide-binding protein and soluble CD14. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2744–2748. doi: 10.1073/pnas.90.7.2744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Savedra R., Jr, Delude R. L., Ingalls R. R., Fenton M. J., Golenbock D. T. Mycobacterial lipoarabinomannan recognition requires a receptor that shares components of the endotoxin signaling system. J Immunol. 1996 Sep 15;157(6):2549–2554. [PubMed] [Google Scholar]
  27. Schumann R. R., Leong S. R., Flaggs G. W., Gray P. W., Wright S. D., Mathison J. C., Tobias P. S., Ulevitch R. J. Structure and function of lipopolysaccharide binding protein. Science. 1990 Sep 21;249(4975):1429–1431. doi: 10.1126/science.2402637. [DOI] [PubMed] [Google Scholar]
  28. Simpson J. A., Smith S. E., Dean R. T. Alginate inhibition of the uptake of Pseudomonas aeruginosa by macrophages. J Gen Microbiol. 1988 Jan;134(1):29–36. doi: 10.1099/00221287-134-1-29. [DOI] [PubMed] [Google Scholar]
  29. Soell M., Lett E., Holveck F., Schöller M., Wachsmann D., Klein J. P. Activation of human monocytes by streptococcal rhamnose glucose polymers is mediated by CD14 antigen, and mannan binding protein inhibits TNF-alpha release. J Immunol. 1995 Jan 15;154(2):851–860. [PubMed] [Google Scholar]
  30. Tobias P. S., Soldau K., Gegner J. A., Mintz D., Ulevitch R. J. Lipopolysaccharide binding protein-mediated complexation of lipopolysaccharide with soluble CD14. J Biol Chem. 1995 May 5;270(18):10482–10488. doi: 10.1074/jbc.270.18.10482. [DOI] [PubMed] [Google Scholar]
  31. Weidemann B., Brade H., Rietschel E. T., Dziarski R., Bazil V., Kusumoto S., Flad H. D., Ulmer A. J. Soluble peptidoglycan-induced monokine production can be blocked by anti-CD14 monoclonal antibodies and by lipid A partial structures. Infect Immun. 1994 Nov;62(11):4709–4715. doi: 10.1128/iai.62.11.4709-4715.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wright S. D., Ramos R. A., Tobias P. S., Ulevitch R. J., Mathison J. C. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 1990 Sep 21;249(4975):1431–1433. doi: 10.1126/science.1698311. [DOI] [PubMed] [Google Scholar]
  33. Zarewych D. M., Kindzelskii A. L., Todd R. F., 3rd, Petty H. R. LPS induces CD14 association with complement receptor type 3, which is reversed by neutrophil adhesion. J Immunol. 1996 Jan 15;156(2):430–433. [PubMed] [Google Scholar]

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

RESOURCES