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Effect of staphylococcal alpha-toxin on phagocytosis of staphylococci by human polymorphonuclear leukocytes
Abstract:
Evidence is presented which shows that alpha-toxin elaborated by Staphylococcus aureus can affect certain of the biological functions of human polymorphonuclear leukocytes (PMN). The pretreatment of PMNs with low doses (less than 10 hemolytic units) of purified toxin enhanced their ability to phagocytose and to kill serum-opsonized staphylococci. At higher doses (greater than or equal to 10 hemolytic units), a certain amount of cell damage was caused (detectable by trypan blue uptake), which resulted in a reduction of their phagocytic capacity. These effects were not seen either with heat-inactivated (60 degrees C, 30 min) or with antibody-neutralized toxin. It is thought that the toxin can bind onto the membrane of the PMN, either exposing additional receptor sites for opsonized bacteria or speeding up the transport of staphylococci across the membrane. Once ingested, the bacteria were more readily killed by the PMNs.
Insights
Staphylococcus aureus alpha-toxin can enhance human polymorphonuclear leukocyte (PMN) functions at low doses, improving bacterial phagocytosis and killing. Higher toxin doses, however, impair PMN function due to cell damage.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Staphylococcus aureus is a significant human pathogen.
- Polymorphonuclear leukocytes (PMNs) are crucial immune cells for combating bacterial infections.
- Bacterial toxins can modulate host immune responses.
Purpose of the Study:
- To investigate the effects of Staphylococcus aureus alpha-toxin on human PMN functions.
- To determine the dose-dependent impact of alpha-toxin on PMN phagocytosis and bacterial killing.
Main Methods:
- Human PMNs were pretreated with varying doses of purified Staphylococcus aureus alpha-toxin.
- Phagocytosis and killing of serum-opsonized staphylococci by PMNs were assessed.
- Cell damage was evaluated using trypan blue uptake.
- Effects of heat-inactivated or antibody-neutralized toxin were examined.
Main Results:
- Low doses of alpha-toxin (<10 hemolytic units) enhanced PMN phagocytosis and killing of opsonized staphylococci.
- Higher doses (>=10 hemolytic units) induced PMN cell damage, reducing phagocytic capacity.
- Inactivated or neutralized toxin did not elicit these effects.
Conclusions:
- Staphylococcus aureus alpha-toxin modulates human PMN functions in a dose-dependent manner.
- Low alpha-toxin concentrations can potentiate PMN antimicrobial activity.
- High alpha-toxin concentrations are cytotoxic to PMNs, impairing their function.