Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 May;64(5):1762–1769. doi: 10.1128/iai.64.5.1762-1769.1996

Human monocyte CD14 is upregulated by lipopolysaccharide.

R Landmann 1, H P Knopf 1, S Link 1, S Sansano 1, R Schumann 1, W Zimmerli 1
PMCID: PMC173990  PMID: 8613389

Abstract

Membrane CD14 is involved in lipopolysaccharide (LPS)-induced monocyte activation; it binds LPS, and antibodies against CD14 block the effects of low-dose LPS. It is unknown how LPS regulates its own receptor CD14 in vitro. Therefore, we investigated the effects of LPS on CD14 mRNA and membrane and soluble CD14 (mCD14 and sCD14, respectively) in human monocytes and macrophages. No changes were observed during the first 3 h of LPS stimulation. After 6 to 15 h, LPS weakly reduced CD14 mRNA and mCD14 and transiently enhanced sCD14 release. A 2-day incubation with LPS caused increases in the levels of CD14 mRNA (2-fold), mCD14 (2-fold), sCD14 (1.5-fold), and LPS-fluorescein isothiocyanate binding (1.5-fold); a 5-h incubation with LPS was sufficient to induce the late effects on mCD14 and sCD14. The maximal effect on mCD14 and sCD14 was reached with > or = 1 ng of LPS per ml; the proportional distribution of the two sCD14 isoforms was not modified by LPS. Besides rough and smooth LPS, lipid A, heat-killed Escherichia coli, lipoteichoic acid, and Staphylococcus aureus cell wall extract (10 micrograms/ml) caused similar increases of mCD14. The LPS effect was blocked by polymyxin B but not by anti-tumor necrosis factor alpha, anti-interleukin-6, anti-gamma interferon, and anti-LPS-binding protein. LPS-induced tumor necrosis factor alpha production was abolished after a second 4-h challenge. In contrast, the LPS-induced increases CD14 mRNA, mCD14, and sCD14 were stronger and appeared earlier after a second LPS challenge. In conclusion, CD14 is transcriptionally upregulated by LPS and other bacterial cell wall constituents.

Full Text

The Full Text of this article is available as a PDF (376.6 KB).

Selected References

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

  1. Bazil V., Baudys M., Hilgert I., Stefanová I., Low M. G., Zbrozek J., Horejsí V. Structural relationship between the soluble and membrane-bound forms of human monocyte surface glycoprotein CD14. Mol Immunol. 1989 Jul;26(7):657–662. doi: 10.1016/0161-5890(89)90048-5. [DOI] [PubMed] [Google Scholar]
  2. Bazil V., Strominger J. L. Shedding as a mechanism of down-modulation of CD14 on stimulated human monocytes. J Immunol. 1991 Sep 1;147(5):1567–1574. [PubMed] [Google Scholar]
  3. Blanchard D. K., Djeu J. Y., Klein T. W., Friedman H., Stewart W. E., 2nd Interferon-gamma induction by lipopolysaccharide: dependence on interleukin 2 and macrophages. J Immunol. 1986 Feb 1;136(3):963–970. [PubMed] [Google Scholar]
  4. Bufler P., Stiegler G., Schuchmann M., Hess S., Krüger C., Stelter F., Eckerskorn C., Schütt C., Engelmann H. Soluble lipopolysaccharide receptor (CD14) is released via two different mechanisms from human monocytes and CD14 transfectants. Eur J Immunol. 1995 Feb;25(2):604–610. doi: 10.1002/eji.1830250244. [DOI] [PubMed] [Google Scholar]
  5. DeForge L. E., Remick D. G. Kinetics of TNF, IL-6, and IL-8 gene expression in LPS-stimulated human whole blood. Biochem Biophys Res Commun. 1991 Jan 15;174(1):18–24. doi: 10.1016/0006-291x(91)90478-p. [DOI] [PubMed] [Google Scholar]
  6. Dentener M. A., Bazil V., Von Asmuth E. J., Ceska M., Buurman W. A. Involvement of CD14 in lipopolysaccharide-induced tumor necrosis factor-alpha, IL-6 and IL-8 release by human monocytes and alveolar macrophages. J Immunol. 1993 Apr 1;150(7):2885–2891. [PubMed] [Google Scholar]
  7. Durieux J. J., Vita N., Popescu O., Guette F., Calzada-Wack J., Munker R., Schmidt R. E., Lupker J., Ferrara P., Ziegler-Heitbrock H. W. The two soluble forms of the lipopolysaccharide receptor, CD14: characterization and release by normal human monocytes. Eur J Immunol. 1994 Sep;24(9):2006–2012. doi: 10.1002/eji.1830240911. [DOI] [PubMed] [Google Scholar]
  8. Fearns C., Kravchenko V. V., Ulevitch R. J., Loskutoff D. J. Murine CD14 gene expression in vivo: extramyeloid synthesis and regulation by lipopolysaccharide. J Exp Med. 1995 Mar 1;181(3):857–866. doi: 10.1084/jem.181.3.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Gallay P., Jongeneel C. V., Barras C., Burnier M., Baumgartner J. D., Glauser M. P., Heumann D. Short time exposure to lipopolysaccharide is sufficient to activate human monocytes. J Immunol. 1993 Jun 1;150(11):5086–5093. [PubMed] [Google Scholar]
  11. Haziot A., Chen S., Ferrero E., Low M. G., Silber R., Goyert S. M. The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage. J Immunol. 1988 Jul 15;141(2):547–552. [PubMed] [Google Scholar]
  12. Heumann D., Gallay P., Barras C., Zaech P., Ulevitch R. J., Tobias P. S., Glauser M. P., Baumgartner J. D. Control of lipopolysaccharide (LPS) binding and LPS-induced tumor necrosis factor secretion in human peripheral blood monocytes. J Immunol. 1992 Jun 1;148(11):3505–3512. [PubMed] [Google Scholar]
  13. Hmama Z., Mey A., Normier G., Binz H., Revillard J. P. CD14 and CD11b mediate serum-independent binding to human monocytes of an acylpolygalactoside isolated from Klebsiella pneumoniae. Infect Immun. 1994 May;62(5):1520–1527. doi: 10.1128/iai.62.5.1520-1527.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Knopf H. P., Otto F., Engelhardt R., Freudenberg M. A., Galanos C., Herrmann F., Schumann R. R. Discordant adaptation of human peritoneal macrophages to stimulation by lipopolysaccharide and the synthetic lipid A analogue SDZ MRL 953. Down-regulation of TNF-alpha and IL-6 is paralleled by an up-regulation of IL-1 beta and granulocyte colony-stimulating factor expression. J Immunol. 1994 Jul 1;153(1):287–299. [PubMed] [Google Scholar]
  15. 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]
  16. Labeta M. O., Durieux J. J., Spagnoli G., Fernandez N., Wijdenes J., Herrmann R. CD14 and tolerance to lipopolysaccharide: biochemical and functional analysis. Immunology. 1993 Nov;80(3):415–423. [PMC free article] [PubMed] [Google Scholar]
  17. Landmann R., Fisscher A. E., Obrecht J. P. Interferon-gamma and interleukin-4 down-regulate soluble CD14 release in human monocytes and macrophages. J Leukoc Biol. 1992 Sep;52(3):323–330. doi: 10.1002/jlb.52.3.323. [DOI] [PubMed] [Google Scholar]
  18. Landmann R., Ludwig C., Obrist R., Obrecht J. P. Effect of cytokines and lipopolysaccharide on CD14 antigen expression in human monocytes and macrophages. J Cell Biochem. 1991 Dec;47(4):317–329. doi: 10.1002/jcb.240470406. [DOI] [PubMed] [Google Scholar]
  19. Landmann R., Scherer F., Schumann R., Link S., Sansano S., Zimmerli W. LPS directly induces oxygen radical production in human monocytes via LPS binding protein and CD14. J Leukoc Biol. 1995 Mar;57(3):440–449. doi: 10.1002/jlb.57.3.440. [DOI] [PubMed] [Google Scholar]
  20. Landmann R., Wesp M., Dukor P. Modulation of interferon-gamma-induced major histocompatibility (MHC) and CD14 antigen changes by lipophilic muramyltripeptide MTP-PE in human monocytes. Cell Immunol. 1988 Nov;117(1):45–55. doi: 10.1016/0008-8749(88)90075-5. [DOI] [PubMed] [Google Scholar]
  21. Landmann R., Zimmerli W., Sansano S., Link S., Hahn A., Glauser M. P., Calandra T. Increased circulating soluble CD14 is associated with high mortality in gram-negative septic shock. J Infect Dis. 1995 Mar;171(3):639–644. doi: 10.1093/infdis/171.3.639. [DOI] [PubMed] [Google Scholar]
  22. Leeuwenberg J. F., Dentener M. A., Buurman W. A. Lipopolysaccharide LPS-mediated soluble TNF receptor release and TNF receptor expression by monocytes. Role of CD14, LPS binding protein, and bactericidal/permeability-increasing protein. J Immunol. 1994 May 15;152(10):5070–5076. [PubMed] [Google Scholar]
  23. Luchi M., Munford R. S. Binding, internalization, and deacylation of bacterial lipopolysaccharide by human neutrophils. J Immunol. 1993 Jul 15;151(2):959–969. [PubMed] [Google Scholar]
  24. Maliszewski C. R. CD14 and immune response to lipopolysaccharide. Science. 1991 May 31;252(5010):1321–1322. doi: 10.1126/science.1718034. [DOI] [PubMed] [Google Scholar]
  25. Marchant A., Duchow J., Delville J. P., Goldman M. Lipopolysaccharide induces up-regulation of CD14 molecule on monocytes in human whole blood. Eur J Immunol. 1992 Jun;22(6):1663–1665. doi: 10.1002/eji.1830220650. [DOI] [PubMed] [Google Scholar]
  26. Matsuura K., Ishida T., Setoguchi M., Higuchi Y., Akizuki S., Yamamoto S. Upregulation of mouse CD14 expression in Kupffer cells by lipopolysaccharide. J Exp Med. 1994 May 1;179(5):1671–1676. doi: 10.1084/jem.179.5.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Newman S. L., Chaturvedi S., Klein B. S. The WI-1 antigen of Blastomyces dermatitidis yeasts mediates binding to human macrophage CD11b/CD18 (CR3) and CD14. J Immunol. 1995 Jan 15;154(2):753–761. [PubMed] [Google Scholar]
  28. Pedron T., Girard R., Turco S. J., Chaby R. Phosphatidylinositol-anchored molecules and inducible lipopolysaccharide binding sites of human and mouse bone marrow cells. J Biol Chem. 1994 Jan 28;269(4):2426–2432. [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. 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]
  32. Ulevitch R. J., Tobias P. S. Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin. Annu Rev Immunol. 1995;13:437–457. doi: 10.1146/annurev.iy.13.040195.002253. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. Zhang Y., Doerfler M., Lee T. C., Guillemin B., Rom W. N. Mechanisms of stimulation of interleukin-1 beta and tumor necrosis factor-alpha by Mycobacterium tuberculosis components. J Clin Invest. 1993 May;91(5):2076–2083. doi: 10.1172/JCI116430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ziegler-Heitbrock H. W., Schraut W., Wendelgass P., Ströbel M., Sternsdorf T., Weber C., Aepfelbacher M., Ehlers M., Schütt C., Haas J. G. Distinct patterns of differentiation induced in the monocytic cell line Mono Mac 6. J Leukoc Biol. 1994 Jan;55(1):73–80. doi: 10.1002/jlb.55.1.73. [DOI] [PubMed] [Google Scholar]
  37. Ziegler-Heitbrock H. W., Wedel A., Schraut W., Ströbel M., Wendelgass P., Sternsdorf T., Bäuerle P. A., Haas J. G., Riethmüller G. Tolerance to lipopolysaccharide involves mobilization of nuclear factor kappa B with predominance of p50 homodimers. J Biol Chem. 1994 Jun 24;269(25):17001–17004. [PubMed] [Google Scholar]

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

RESOURCES