Activation of Mononuclear Immune Cells in Response to Staphylococcal Lipoteichoic Acid

Ohshima, Yukio; Ko, H.L.; Beuth, Josef; Burrichter, H.; Oette, K.; Pulverer, G.

doi:10.1016/s0934-8840(11)80303-8

Cited by 7 publications

(6 citation statements)

References 25 publications

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“…No structural equivalent to LPS has been clearly identified in gram-positive bacteria, although the inflammatory immune response to gram-negative and gram-positive bacteria can hardly be distinguished by the symptoms. Recently lipoteichoic acids (LTA) from the cytoplasmic membrane of gram-positive bacteria (7) have become increasingly recognized as an immunostimulatory principle (1,5,10,18,25,26,32). For example, commercial preparations of LTA from Staphylococcus aureus were shown to exhibit potent immunostimulation in vitro (3,11) and in vivo (4).…”

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confidence: 99%

Structural Decomposition and Heterogeneity of Commercial Lipoteichoic Acid Preparations

et al. 2002

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Fractionation of commercial preparations of lipoteichoic acids (LTA) by hydrophobic interaction chromatography (HIC) and nuclear magnetic resonance spectroscopy revealed very inhomogeneous compositions and decomposition of the LTA structure: LTA content of the preparations averaged 61% for Streptococcus pyogenes, 16% for Bacillus subtilis, and 75% for Staphylococcus aureus. The decomposition was characterized by a loss of glycerophosphate units as well as alanine and N-acetylglucosamine substituents. All preparations containedto varying degrees-non-LTA, non-lipopolysaccharide (LPS) immunostimulatory components as indicated by their elution profile in HIC, lack of phosphate, and negative Limulus amoebocyte lysate (LAL) test results. After purification, the commercial LTA from Bacillus subtilis and S. pyogenes but not LTA from S. aureus induced the release of tumor necrosis factor alpha, interleukin 1 beta (IL-1␤), IL-6, and IL-10 in human blood. While pure LTA are negative in the LAL assay, endotoxin equivalents of more than 10 ng of LPS/mg of LTA were found in the commercial preparations. Taken together, these data indicate that these crude preparations with relatively high endotoxin contamination are not suitable for characterizing the activation of immune cells by LTA.Gram-negative bacteria are recognized by the innate immune system via their endotoxins, i.e., lipopolysaccharides (LPS), which are components of the outer membrane (28). No structural equivalent to LPS has been clearly identified in gram-positive bacteria, although the inflammatory immune response to gram-negative and gram-positive bacteria can hardly be distinguished by the symptoms. Recently lipoteichoic acids (LTA) from the cytoplasmic membrane of gram-positive bacteria (7) have become increasingly recognized as an immunostimulatory principle (1,5,10,18,25,26,32). For example, commercial preparations of LTA from Staphylococcus aureus were shown to exhibit potent immunostimulation in vitro (3, 11) and in vivo (4).It was demonstrated, however, that a potent immunostimulatory nonhydrophobic phosphate-containing fraction can be separated from commercially available S. aureus LTA by reverse-phase chromatography (20, 21); the resulting purified LTA had no immunostimulatory potential but instead inhibited CD14-mediated activation of monocytes by LPS. Also, separation of immunostimulatory glycerophosphate-containing glycolipid fractions from otherwise inactive LTA was reported for Enterococcus hirae (13,14,31,34), employing, in sequence, hydrophobic interaction chromatography (HIC) and anion exchange chromatography on DEAE. The latter findings raised doubts as to the immunostimulatory potential of LTA in general. However, we have shown recently that decomposition of LTA from S. aureus during phenol extraction results in the loss of its immunostimulatory potential. We developed a gentler extraction procedure using butanol, which yielded bioactive, pure LTA (24). A recent report (9) again raised the problem of endotoxin contamination of commercial LTA p...

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Structural Decomposition and Heterogeneity of Commercial Lipoteichoic Acid Preparations

et al. 2002

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“…The lectin-mediated activation of lymphatic cells was comparable with the IL-l-induced activation, which represents a potent standard stimulus for these cells in immunologic studies [15,16]. Since IL-2 receptors and HLA-DQ antigens are induced on T and/or B cells when appropriately presented antigens, mitogens, or antibodies interact with the adequate receptor complex, ML-1 can be suggested to be a potent stimulus.…”

Section: Discussionmentioning

confidence: 66%

“…Both IL-2 and IL-2 receptors play a critical role in the evolution of specialized T-cell populations necessary to mount a normal T-cell response [20]. IL-2 receptors are not detectable on freshly isolated T and/or B cells and generally appear after polyclonal activation, e.g., of the T-cell receptor [16,21]. Similarly, the expression of HLA-DQ antigens can be induced on resting B-cells and represents a differentiation and activation marker for this cell line [14].…”

Section: Discussionmentioning

confidence: 99%

“…Cell suspensions (2 x 105 cells/0.2 ml medium) from healthy donors (n = 5) were incubated in the presence of serial dilutions (1.6-0.006 ng) of the galactosidespecific lectin from mistletoe (ML-I) in a microculture system in an atmosphere of 5% CO2 for 72 h. To evaluate the status of activity by assessment of the presence of selected surface markers, immunofluorescence staining was performed using fluorescence-conjugated monoclonal antibodies (CD-25/anti-interleukin (I1)-2 receptor and anti-HLA-DQ; Becton-Dickinson, Heidelberg, FRG). A fluorescence-activated cell sorter (FACS, Becton-Dickinson) was used for analysis of the status of cellular activity, ascribing the expression of IL-2 and HLA-DQ receptors primarily to T and B lymphocytes, respectively, and IL-1 was used as the positive control [13,16].…”

Section: In Vitro Lymphocyte Activationmentioning

confidence: 99%

“…Peripheral blood lymphocytes (PBL) were separated by standard methods, as previously described [1,16]. The immunofluorescence staining of PBL was performed using fluorescence-conjugated monoclonal antibodies (Leu 4, T lymphocytes; Leu 2, cytotoxic/suppressor T lymphocytes; Leu 3, helper/inducer T lymphocytes; Leu 12, B lymphocytes; Leu 11 and 19, NK cells; CD-25, anti IL-2 receptor; all obtained from Becton-Dickinson).…”

Section: Immunomodulating Activity Of the Galactoside-specific Lectinmentioning

confidence: 99%

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Behavior of lymphocyte subsets and expression of activation markers in response to immunotherapy with galactoside-specific lectin from mistletoe in breast cancer patients

Beuth

Gabius

et al. 1992

Clin Investig

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Cellular aspects of the immunomodulating activity of the galactoside-specific lectin from mistletoe (ML-1) were investigated in 10 cancer patients. Regular subcutaneous injections (4 weeks) of the optimal dosis of ML-1 (1 ng per kg body weight, twice a week) yielded notable increases in the apparent numbers of certain lymphocyte subsets [pan T cells; helper T cells; natural killer (NK) cells] which are generally believed to be involved in antitumor immunity. Moreover, ML-1 administration resulted in an increased level of expression of interleukin (IL)2 receptors on lymphatic cells, an indicator of cellular activation. In vitro, the exposure of human lymphocytes to ML-1 resulted in an enhanced expression of receptors for IL-2 (T cells) and HLA-DQ (B cells), which similarly substantiated the capacity of ML-1 to affect immunological parameters within the host defense system. Thorough clinical trials are now required to assess any impact of the application of the lectin on the course of the disease.

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Teichoic Acids of Gram-positive Bacteria

Hancock

2002

Molecular Medical Microbiology

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Activation of Mononuclear Immune Cells in Response to Staphylococcal Lipoteichoic Acid

Cited by 7 publications

References 25 publications

Structural Decomposition and Heterogeneity of Commercial Lipoteichoic Acid Preparations

Structural Decomposition and Heterogeneity of Commercial Lipoteichoic Acid Preparations

Behavior of lymphocyte subsets and expression of activation markers in response to immunotherapy with galactoside-specific lectin from mistletoe in breast cancer patients

Teichoic Acids of Gram-positive Bacteria

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