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Glycoconjugates prevent B. anthracis toxin-induced cell death through binding while activating macrophages

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Abstract

Bacillus anthracis toxins may be attenuated if macrophages could neutralize toxins upon contact or exposure. Glycoconjugate-bearing polymers, which have been shown to bind to Bacillus spores, were tested for recognition and binding of protective antigen (PA), lethal factor (LF), and edema factor (EF) toxins. We have demonstrated modulation of macrophage activity following exposure to these toxins. Without glycoconjugate (GC) activation, murine macrophages were killed by Bacillus toxins. GCs were shown to have a protective influence, sparing macrophages from toxin-induced cell death, as shown by increased macrophage cell viability based on trypan blue assay. Increased levels of inducible nitric oxide (NO) production by macrophages in presence of GCs suggest that GCs provide an activation signal for macrophages and stimulate their function. Results hint to GCs that promote neutralization of Bacillus toxins, block toxin-induced macrophage death, while increasing macrophage activation. Polymeric GCs may suggest novel approaches to improve existing or develop new vaccines as well as immunotherapeutics.

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Abbreviations

Glyc-PAA-flu:

Glycoconjugate-polyacrylamide-fluorescein polymer

GC(s):

Glycoconjugate(s)

GC1:

Galα1-3 GalNAcα -PAA-flu

GC2:

Galβ1-3 GalNAcβ-PAA-flu

GC3:

GalNAcα1-3 GalNAcβ -PAA-flu

GC4:

Galβ1-3 Galβ -PAA-flu

GC5:

GlcNAcβ1-4 GlcNAcβ -PAA-flu

GC6:

Fucα1-4 GlcNAcβ -PAA-flu

GC7:

Galβ1-2 Galβ -PAA-flu

GC8:

Fucα1-3 GlcNAcβ -PAA-flu

GC9:

GlcNAcβ1-3 GlcNAcα -PAA-flu

GC10:

GalNAcβ1-6 GalNAcα -PAA-flu

Gal:

Galactose

GalNAc:

N-acetylgalactosamine

Fuc:

Fucose

GlcNAc:

N-acetylglucosamine

PAA:

Polyacrylamide

Flu:

Fluorescein

LDH:

Lactate dehydrogenase

NO:

Nitric oxide

CFU:

Colony forming units

M:

Macrophages

PA:

Protective antigen

LF:

Lethal factor

EF:

Edema factor

ATR:

Anthrax toxin receptor

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Acknowledgements

The present study was supported in part by start-up funds and the Kathleen Thomsen Hall Charitable Trust Grant awarded to Tarasenko. This study conforms to the IBC protocol # 09049, the UALR IACUC protocol # R-09-01 and the UAMS IACUC protocol # 2985. The authors extend their appreciation to editors and reviewers, whose comments and suggestions were most helpful in making this manuscript a more solid one for publication in the Glycoconjugate Journal.

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Authors and Affiliations

  1. Department of Biology, University of Arkansas at Little Rock, 2801 South University Ave., Little Rock, AR, 72204, USA

    Olga Tarasenko

  2. Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Ashley Scott & Lee Soderberg

  3. Bioinformatics Program, University of Arkansas at Little Rock, 2801 South University Ave., Little Rock, AR, 72204, USA

    Pierre Alusta

  4. Bioinformatics Program, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Pierre Alusta

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  1. Olga Tarasenko
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  2. Ashley Scott
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  4. Pierre Alusta
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Correspondence to Olga Tarasenko.

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Tarasenko, O., Scott, A., Soderberg, L. et al. Glycoconjugates prevent B. anthracis toxin-induced cell death through binding while activating macrophages. Glycoconj J 29, 25–33 (2012). https://doi.org/10.1007/s10719-011-9360-3

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