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Related Experiment Videos

Antitoxin activity of human polymorphonuclear leucocytes.

H E Larson, G P Smith, L Shah

    British Journal of Experimental Pathology
    |April 1, 1985
    PubMed
    Summary

    Human white blood cells, polymorphonuclear leucocytes (PMNL), effectively neutralize bacterial toxins like Clostridium difficile cytotoxin. This innate immune defense mechanism involves enzymes within PMNL granules, highlighting their role in combating exotoxins.

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    Area of Science:

    • Immunology
    • Microbiology
    • Cell Biology

    Background:

    • Bacterial exotoxins pose significant health risks.
    • The innate immune system, particularly white blood cells, plays a crucial role in neutralizing pathogens and their toxins.
    • Polymorphonuclear leucocytes (PMNL) are key components of the innate immune response.

    Purpose of the Study:

    • To investigate the capacity of human polymorphonuclear leucocytes (PMNL) to inactivate specific bacterial exotoxins.
    • To identify the cellular components and mechanisms responsible for PMNL's antitoxin activity.
    • To determine the potential role of PMNL as a primary defense against bacterial toxins.

    Main Methods:

    • Incubation of PMNL (whole cells and sonicated suspensions) with Clostridium difficile cytotoxin and Clostridium perfringens toxins.

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  • Testing of mononuclear cell fractions for antitoxin activity.
  • Sucrose density gradient fractionation of PMNL to isolate active components.
  • Assessment of toxin inactivation in the presence of protease inhibitors.
  • Comparison of PMNL activity with purified chymotrypsin.

    • Main Results:

    • PMNL effectively inactivated Clostridium difficile cytotoxin and Clostridium perfringens phospholipase C, but not C. perfringens enterotoxin.
    • Antitoxin activity was associated with PMNL, not mononuclear cells, and correlated with cell concentration.
    • The highest PMNL concentrations completely inactivated C. difficile cytotoxin within 2 minutes.
    • Fractionation localized antitoxin activity to myeloperoxidase within PMNL's primary granules.
    • Protease inhibitors blocked toxin inactivation, suggesting a role for neutral proteases.
    • PMNL demonstrated greater activity against C. difficile cytotoxin than purified chymotrypsin.

    Conclusions:

    • Human PMNL possess significant antitoxin activity against specific bacterial exotoxins, notably C. difficile cytotoxin.
    • The antitoxin activity is mediated by neutral proteases located in the primary granules of PMNL.
    • PMNL represent a critical component of the innate immune system's defense against certain bacterial toxins.