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absence of neutrophil in C. perfringens?

Discussion in 'Step I' started by MudPhud20XX, Sep 27, 2014.

  1. MudPhud20XX

    MudPhud20XX 2+ Year Member

    Nov 25, 2013
    One of the questions I did presented a clinical vignette of C. perfringens and asked what you would see from the debrided tissue under microscopy and the answer was the absence of neutrophils. But the solution did not really explain why? How come you get no neutrophils with C. perfringens? Can anyone explain this please? Thank you. Below is the explanation.

    "Traumatic gas gangrene is a fulminant disease, typically caused by Clostridium perfringens type A and characterized by extensive tissue destruction rapidly progressing to shock and death. Muscle biopsy in clostridial gas gangrene reveals large Gram-positive rods with truncated ends and a striking paucity of leukocyte infiltration."
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  3. Silo004

    Silo004 5+ Year Member

    Mar 5, 2011
    Alpha toxin stops them right in their tracks. Lecithinase destroys cell walls.
  4. Transposony

    Transposony Do or do not, There is no try 5+ Year Member

    Nov 10, 2011
    The mechanism:
    1. Alpha toxin activate the platelet adhesion molecule gpIIb/IIIa leading to platelet aggregation causing occlusion of blood vessels.
    2. Alpha toxin induced upregulation of leukocyte CD11b/CD18 integrins.
    3. Alpha toxin–induced upregulation of platelet P-selectin and its binding to leukocyte P-selectin glycoprotein ligand-1.
    4. The platelets interaction with neutrophils (step 3 above) , produce intermediates in lipoxin synthesis.
    5. The lipoxins inhibit leukocyte recruitment, chemotaxis and adhesion to endothelium.
    6. Alpha toxin also stimulated production of endothelial cell derived IL-8. High concentrations of IL-8 causes reduced diapedesis & transmigration of leukocytes through endothelium.

    It's like a hostage situation-they accumulate all around it but can't get in and if any of them manage to get in, get's killed.
    nrimbbs, DeeJay2728, seminoma and 2 others like this.
  5. seminoma

    seminoma 2+ Year Member

    Aug 9, 2014
    Haven't heard about IL-8 causes reduced diapedesis. Where'd you read that?
  6. Transposony

    Transposony Do or do not, There is no try 5+ Year Member

    Nov 10, 2011
    I apologize for not explaining it more clearly. Under "normal" circumstances IL-8 causes chemotaxis, diapedesis & transmigration of leukocytes.
    However, in Gas gangrene, alpha toxin stimulates increased production of IL-8 causing reduced diapedesis & transmigration of leukocytes. A phenomenon described as “heterologous desensitization”.
    Basically, alpha toxin upregulates the entire inflammatory process and makes everything "sticky". Platelets , endothelium, neutrophils stick to each other causing thrombosis, and neutrophils can't get to the site of action being stuck to endothelium and platelets.
    Last edited: Sep 29, 2014
    DeeJay2728 and seminoma like this.

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