Comparative toxicity of the horse eosinophil peroxidase-H2O2-halide system and granule basic proteins.
Abstract: Stimulated eosinophils release cytotoxic granule constituents, including eosinophil peroxidase (EPO) and a group of granule basic proteins (GBP). EPO reacts with H2O2 formed by the respiratory burst and a halide to form cytotoxic oxidants. The relative potency of the EPO-H2O2-halide system and the GBP is considered here. Horse eosinophils were induced to degranulate, the degranulation products were separated by chromatography on Sephadex G-50 and comparable volumes of the column fractions were tested for toxicity to Escherichia coli and the schistosomula of Schistosoma mansoni in the presence and absence of H2O2 and halides. Both the EPO system and GBP were toxic. However, the peak EPO fraction could be diluted 1000-fold at pH 7.0 and 5000-fold at pH 5.0, and with a 10-fold dilution at pH 7.0 incubation time could be reduced to 5 s, with retention of bactericidal activity in the presence of H2O2 and halides, whereas the peak GBP fractions diluted 10-fold had a small bactericidal effect at 1 h which increased with prolongation of incubation to 24 h. A less than 1 log fall in E. coli viable cell count was produced by the GBP fractions under all conditions as compared to total destruction (greater than 5 log fall) with the EPO system. A 1000-fold dilution of the peak EPO fraction was schistosomulocidal in the presence of H2O2 and halides, with toxicity observed at 2 h with a 10-fold dilution. In contrast, no schistosomulocidal activity was observed at 18 h with a 10-fold dilution of the GBP fractions. However, toxicity was observed with a 5- or 50-fold increase in GBP concentration with maximum toxicity observed with fractions between the two major protein peaks. Thus, under the conditions employed, the EPO-H2O2-halide system contributed to a considerably greater degree to the toxic activity of the granule components than did the GBP.
Publication Date: 1989-07-01 PubMed ID: 2659666
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- Comparative Study
- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research article discusses the comparative toxic effects of eosinophil peroxidase (EPO), a constituent of eosinophil granules, and granule basic proteins (GBP) on bacteria and parasitic organisms. The study reveals that the EPO-H2O2-halide system shows much greater toxicity than GBP.
Understanding Eosinophil Peroxidase and Granule Basic Proteins
- The eosinophil is a type of white blood cell that plays a key role in our body’s immune response, particularly during allergic reactions and parasitic infections.
- When these cells are stimulated, they release a range of cytotoxic (cell-killing) granule constituents. Two of these are eosinophil peroxidase (EPO) and granule basic proteins (GBP).
- EPO reacts with hydrogen peroxide (H2O2) and a halide to form cytotoxic oxidants. Conversely, GBP are a group of proteins present in the granules of eosinophils.
Methodology and Results
- The study involved inducing horse eosinophils to degranulate, or release their granule contents. These degranulation products were then separated by chromatography, and tested for toxicity against Escherichia coli (a bacteria) and schistosomula (larvae) of Schistosoma mansoni (a parasitic worm).
- Both EPO and GBP demonstrated toxicity against bacteria. However, the EPO system appeared much more potent, even at considerable dilutions and short exposure times, compared to GBP.
- The results showed that while diluted GBP fractions had a small bactericidal effect over a prolonged period of 24 hours, the EPO system could destroy bacteria with just 5 seconds of exposure at pH 7.0.
- GBP fractions produced a less than 1 log fall in E. coli viable cell count, whereas EPO system caused a greater than 5 log fall, indicating total bacterial destruction.
- In the presence of H2O2 and halides, a 1000-fold dilution of the peak EPO fraction also showed toxicity against schistosomula, whereas the GBP fractions displayed no schistosomulocidal activity at similar dilutions and even after prolonged incubation.
Conclusion
- Under experimental conditions, the EPO-H2O2-halide system exhibited much higher cytotoxic activity than the GBP. This indicates the greater contribution of the EPO system to the toxic activity of eosinophil granules.
Cite This Article
APA
Klebanoff SJ, Agosti JM, Jörg A, Waltersdorph AM.
(1989).
Comparative toxicity of the horse eosinophil peroxidase-H2O2-halide system and granule basic proteins.
J Immunol, 143(1), 239-244.
Publication
Researcher Affiliations
- Department of Medicine, University of Washington, Seattle 98195.
MeSH Terms
- Animals
- Blood Bactericidal Activity
- Blood Proteins / toxicity
- Bromides / toxicity
- Cytoplasmic Granules / physiology
- Eosinophil Granule Proteins
- Eosinophil Peroxidase
- Eosinophils / enzymology
- Eosinophils / immunology
- Eosinophils / physiology
- Escherichia coli / drug effects
- Escherichia coli / growth & development
- Free Radicals
- Horses
- Hydrogen Peroxide / toxicity
- Peroxidases / toxicity
- Ribonucleases
- Schistosoma mansoni / drug effects
- Schistosoma mansoni / growth & development
- Sodium / toxicity
- Sodium Chloride / toxicity
- Sodium Compounds
Grant Funding
- AI 07044 / NIAID NIH HHS
- AI 07763 / NIAID NIH HHS
- AI 17758 / NIAID NIH HHS
Citations
This article has been cited 13 times.- Lu T, Galijasevic S, Abdulhamid I, Abu-Soud HM. Analysis of the mechanism by which melatonin inhibits human eosinophil peroxidase.. Br J Pharmacol 2008 Jul;154(6):1308-17.
- Swartz JM, Dyer KD, Cheever AW, Ramalingam T, Pesnicak L, Domachowske JB, Lee JJ, Lee NA, Foster PS, Wynn TA, Rosenberg HF. Schistosoma mansoni infection in eosinophil lineage-ablated mice.. Blood 2006 Oct 1;108(7):2420-7.
- Borelli V, Vita F, Shankar S, Soranzo MR, Banfi E, Scialino G, Brochetta C, Zabucchi G. Human eosinophil peroxidase induces surface alteration, killing, and lysis of Mycobacterium tuberculosis.. Infect Immun 2003 Feb;71(2):605-13.
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- Sijtsema NM, Tibbe AG, Segers-Nolten IG, Verhoeven AJ, Weening RS, Greve J, Otto C. Intracellular reactions in single human granulocytes upon phorbol myristate acetate activation using confocal Raman microspectroscopy.. Biophys J 2000 May;78(5):2606-13.
- Lefkowitz DL, Lincoln JA, Howard KR, Stuart R, Lefkowitz SS, Allen RC. Macrophage-mediated candidacidal activity is augmented by exposure to eosinophil peroxidase: a paradigm for eosinophil-macrophage interaction.. Inflammation 1997 Apr;21(2):159-72.
- Dvorak AM, Onderdonk AB, McLeod RS, Monahan-Earley RA, Cullen J, Antonioli DA, Blair JE, Morgan ES, Cisneros RL, Estrella P. Axonal necrosis of enteric autonomic nerves in continent ileal pouches. Possible implications for pathogenesis of Crohn's disease.. Ann Surg 1993 Mar;217(3):260-71.
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- Dvorak AM, Ackerman SJ, Furitsu T, Estrella P, Letourneau L, Ishizaka T. Mature eosinophils stimulated to develop in human-cord blood mononuclear cell cultures supplemented with recombinant human interleukin-5. II. Vesicular transport of specific granule matrix peroxidase, a mechanism for effecting piecemeal degranulation.. Am J Pathol 1992 Apr;140(4):795-807.
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