• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of iaiPermissionsJournals.ASM.orgJournalIAI ArticleJournal InfoAuthorsReviewers
Infect Immun. Jul 1994; 62(7): 2715–2721.
PMCID: PMC302873

Gram-positive cell walls stimulate synthesis of tumor necrosis factor alpha and interleukin-6 by human monocytes.


Purified cell walls representing a wide variety in teichoic acid and peptidoglycan structure prepared from eight different gram-positive bacterial species induced the production of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 from human monocytes in the presence of 10% plasma or serum. Significant amounts of cytokines began to be produced at concentrations above 100 ng to 1 microgram of cell walls per ml, with maximal production requiring 10 to 100 micrograms of cell wall material per ml. In the absence of plasma, the cytokine-inducing capacity of cell wall preparations was lower by at least an order of magnitude. The serum-derived cofactor was inactivated by heating at 90 degrees C for 30 min, suggesting that the activity is associated with a protein. On the other hand, replacement of normal with hypogammaglobulinemic plasma, inactivation of complement (at 56 degrees C), and blockade by the monoclonal antibody MY4 of the CD14 receptors on monocytes did not inhibit the production of TNF-alpha induced by whole cell walls. Cell walls also stimulated production of TNF-alpha induced by whole cell walls. Cell walls also stimulated production of TNF-alpha in the presence of polymyxin B, and macrophages derived from the lipopolysaccharide-insensitive cell line of C3He/HeJ mice also produced this cytokine when stimulated by cell walls. Both peptidoglycan and the soluble glycan-teichoic acid component prepared by an enzymatic method from the same wall preparation exhibited a serum-dependent induction of TNF-alpha from monocytes, while stem peptides and disacharride peptides had only poor, if any, activity. Cell walls may contribute to the septic shock induced by gram-positive bacteria.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Baumgartner JD, Heumann D, Gerain J, Weinbreck P, Grau GE, Glauser MP. Association between protective efficacy of anti-lipopolysaccharide (LPS) antibodies and suppression of LPS-induced tumor necrosis factor alpha and interleukin 6. Comparison of O side chain-specific antibodies with core LPS antibodies. J Exp Med. 1990 Mar 1;171(3):889–896. [PMC free article] [PubMed]
  • Corradin SB, Mauël J, Gallay P, Heumann D, Ulevitch RJ, Tobias PS. Enhancement of murine macrophage binding of and response to bacterial lipopolysaccharide (LPS) by LPS-binding protein. J Leukoc Biol. 1992 Oct;52(4):363–368. [PubMed]
  • Bhakdi S, Klonisch T, Nuber P, Fischer W. Stimulation of monokine production by lipoteichoic acids. Infect Immun. 1991 Dec;59(12):4614–4620. [PMC free article] [PubMed]
  • Burchard KW, Minor LB, Slotman GJ, Gann DS. Staphylococcus epidermidis sepsis in surgical patients. Arch Surg. 1984 Jan;119(1):96–100. [PubMed]
  • Christensen GD, Bisno AL, Parisi JT, McLaughlin B, Hester MG, Luther RW. Nosocomial septicemia due to multiply antibiotic-resistant Staphylococcus epidermidis. Ann Intern Med. 1982 Jan;96(1):1–10. [PubMed]
  • Crass BA, Bergdoll MS. Toxin involvement in toxic shock syndrome. J Infect Dis. 1986 May;153(5):918–926. [PubMed]
  • Dacey RG, Sande MA. Effect of probenecid on cerebrospinal fluid concentrations of penicillin and cephalosporin derivatives. Antimicrob Agents Chemother. 1974 Oct;6(4):437–441. [PMC free article] [PubMed]
  • de Jonge BL, Chang YS, Gage D, Tomasz A. Peptidoglycan composition of a highly methicillin-resistant Staphylococcus aureus strain. The role of penicillin binding protein 2A. J Biol Chem. 1992 Jun 5;267(16):11248–11254. [PubMed]
  • Dinarello CA. Interleukin-1 and interleukin-1 antagonism. Blood. 1991 Apr 15;77(8):1627–1652. [PubMed]
  • Freudenberg MA, Galanos C. Tumor necrosis factor alpha mediates lethal activity of killed gram-negative and gram-positive bacteria in D-galactosamine-treated mice. Infect Immun. 1991 Jun;59(6):2110–2115. [PMC free article] [PubMed]
  • Garcia-Bustos J, Tomasz A. A biological price of antibiotic resistance: major changes in the peptidoglycan structure of penicillin-resistant pneumococci. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5415–5419. [PMC free article] [PubMed]
  • Garcia-Bustos JF, Chait BT, Tomasz A. Structure of the peptide network of pneumococcal peptidoglycan. J Biol Chem. 1987 Nov 15;262(32):15400–15405. [PubMed]
  • Griffin JD, Ritz J, Nadler LM, Schlossman SF. Expression of myeloid differentiation antigens on normal and malignant myeloid cells. J Clin Invest. 1981 Oct;68(4):932–941. [PMC free article] [PubMed]
  • Heumann D, Gallay P, Barras C, Zaech P, Ulevitch RJ, Tobias PS, Glauser MP, Baumgartner JD. 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]
  • Höltje JV, Tomasz A. Specific recognition of choline residues in the cell wall teichoic acid by the N-acetylmuramyl-L-alanine amidase of Pneumococcus. J Biol Chem. 1975 Aug 10;250(15):6072–6076. [PubMed]
  • Ikejima T, Dinarello CA, Gill DM, Wolff SM. Induction of human interleukin-1 by a product of Staphylococcus aureus associated with toxic shock syndrome. J Clin Invest. 1984 May;73(5):1312–1320. [PMC free article] [PubMed]
  • Jupin C, Anderson S, Damais C, Alouf JE, Parant M. Toxic shock syndrome toxin 1 as an inducer of human tumor necrosis factors and gamma interferon. J Exp Med. 1988 Mar 1;167(3):752–761. [PMC free article] [PubMed]
  • Keller R, Fischer W, Keist R, Bassetti S. Macrophage response to bacteria: induction of marked secretory and cellular activities by lipoteichoic acids. Infect Immun. 1992 Sep;60(9):3664–3672. [PMC free article] [PubMed]
  • Keller R, Gustafson JE, Keist R. The macrophage response to bacteria. Modulation of macrophage functional activity by peptidoglycan from Moraxella (Branhamella) catarrhalis. Clin Exp Immunol. 1992 Sep;89(3):384–389. [PMC free article] [PubMed]
  • LACKS S, HOTCHKISS RD. A study of the genetic material determining an enzyme in Pneumococcus. Biochim Biophys Acta. 1960 Apr 22;39:508–518. [PubMed]
  • Martin MA, Pfaller MA, Wenzel RP. Coagulase-negative staphylococcal bacteremia. Mortality and hospital stay. Ann Intern Med. 1989 Jan 1;110(1):9–16. [PubMed]
  • Mathison JC, Tobias PS, Wolfson E, Ulevitch RJ. 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]
  • Mattsson E, Verhage L, Rollof J, Fleer A, Verhoef J, van Dijk H. Peptidoglycan and teichoic acid from Staphylococcus epidermidis stimulate human monocytes to release tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6. FEMS Immunol Med Microbiol. 1993 Oct;7(3):281–287. [PubMed]
  • Miethke T, Wahl C, Heeg K, Echtenacher B, Krammer PH, Wagner H. T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. J Exp Med. 1992 Jan 1;175(1):91–98. [PMC free article] [PubMed]
  • Morrison DC, Jacobs DM. Binding of polymyxin B to the lipid A portion of bacterial lipopolysaccharides. Immunochemistry. 1976 Oct;13(10):813–818. [PubMed]
  • Natanson C, Danner RL, Elin RJ, Hosseini JM, Peart KW, Banks SM, MacVittie TJ, Walker RI, Parrillo JE. Role of endotoxemia in cardiovascular dysfunction and mortality. Escherichia coli and Staphylococcus aureus challenges in a canine model of human septic shock. J Clin Invest. 1989 Jan;83(1):243–251. [PMC free article] [PubMed]
  • Ornelas-Soares A, de Lencastre H, de Jonge B, Gage D, Chang YS, Tomasz A. The peptidoglycan composition of a Staphylococcus aureus mutant selected for reduced methicillin resistance. J Biol Chem. 1993 Dec 15;268(35):26268–26272. [PubMed]
  • Parsonnet J. Mediators in the pathogenesis of toxic shock syndrome: overview. Rev Infect Dis. 1989 Jan-Feb;11 (Suppl 1):S263–S269. [PubMed]
  • Riesenfeld-Orn I, Wolpe S, Garcia-Bustos JF, Hoffmann MK, Tuomanen E. Production of interleukin-1 but not tumor necrosis factor by human monocytes stimulated with pneumococcal cell surface components. Infect Immun. 1989 Jul;57(7):1890–1893. [PMC free article] [PubMed]
  • Schumann RR, Leong SR, Flaggs GW, Gray PW, Wright SD, Mathison JC, Tobias PS, Ulevitch RJ. Structure and function of lipopolysaccharide binding protein. Science. 1990 Sep 21;249(4975):1429–1431. [PubMed]
  • See RH, Chow AW. Staphylococcal toxic shock syndrome toxin 1-induced tumor necrosis factor alpha and interleukin-1 beta secretion by human peripheral blood monocytes and T lymphocytes is differentially suppressed by protein kinase inhibitors. Infect Immun. 1992 Aug;60(8):3456–3459. [PMC free article] [PubMed]
  • Timmerman CP, Mattsson E, Martinez-Martinez L, De Graaf L, Van Strijp JA, Verbrugh HA, Verhoef J, Fleer A. Induction of release of tumor necrosis factor from human monocytes by staphylococci and staphylococcal peptidoglycans. Infect Immun. 1993 Oct;61(10):4167–4172. [PMC free article] [PubMed]
  • Tracey KJ, Lowry SF. The role of cytokine mediators in septic shock. Adv Surg. 1990;23:21–56. [PubMed]
  • Wakabayashi G, Gelfand JA, Jung WK, Connolly RJ, Burke JF, Dinarello CA. Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock-like state and tissue injury in rabbits without endotoxemia. Comparison to Escherichia coli. J Clin Invest. 1991 Jun;87(6):1925–1935. [PMC free article] [PubMed]
  • Wardle N. Bacteraemic and endotoxic shock. Br J Hosp Med. 1979 Jul;22(1):104–104. [PubMed]
  • Wiles JB, Cerra FB, Siegel JH, Border JR. The systemic septic response: does the organism matter? Crit Care Med. 1980 Feb;8(2):55–60. [PubMed]
  • Winkelstein JA, Tomasz A. Activation of the alternative complement pathway by pneumococcal cell wall teichoic acid. J Immunol. 1978 Jan;120(1):174–178. [PubMed]
  • Wright SD, Ramos RA, Patel M, Miller DS. Septin: a factor in plasma that opsonizes lipopolysaccharide-bearing particles for recognition by CD14 on phagocytes. J Exp Med. 1992 Sep 1;176(3):719–727. [PMC free article] [PubMed]
  • Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 1990 Sep 21;249(4975):1431–1433. [PubMed]

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


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...