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Group A streptococcal peptidoglycan-polysaccharide inhibits phagocytic activity of human polymorphonuclear leukocytes
Abstract:
Injection of sterile aqueous preparations of the peptidoglycan-polysaccharide of group A streptococci (PG-APS) produces chronic inflammation in several animal models. Chronic bacterial infection may be involved in some aspects of the pathogenesis of inflammation associated with the accumulation of PG-APS. Accordingly, the effect of PG-APS on human neutrophil (polymorphonuclear leukocyte [PMN]) bactericidal activity was studied with the supposition that this interaction may contribute to the inflammation observed. Concentrations of PG-APS greater than 10 micrograms/ml inhibited the ability of PMNs to kill Staphylococcus aureus. This inhibition was not due to a cytotoxic effect of PG-APS on PMNs, nor did PG-APS inhibit PMN metabolism required for the formation of microbicidal oxygen reduction products. PG-APS concentrations of 10 micrograms/ml or greater in the presence of 10% normal serum inhibited the attachment of bacteria to PMNs by 49% as compared with control cell populations. The concentrations of PG-APS required to inhibit uptake of Staphylococcus aureus were identical to those required for inhibition of PMN bactericidal activity. This inhibition did not occur in the presence of serum-free medium or medium with sera that had been heated to inactivate complement. These results show that PG-APS interacts with serum to inhibit PMN-mediated killing of S. aureus, most probably by interfering with bacterial uptake.
Insights
Group A streptococcal peptidoglycan-polysaccharide (PG-APS) impairs human neutrophil bacterial killing. PG-APS inhibits Staphylococcus aureus uptake by neutrophils, suggesting a role in chronic inflammation.
Area of Science:
- Immunology
- Microbiology
- Pathogenesis
Background:
- Peptidoglycan-polysaccharide (PG-APS) from group A streptococci induces chronic inflammation in animal models.
- Chronic bacterial infections and PG-APS accumulation are implicated in inflammatory disease pathogenesis.
Purpose of the Study:
- To investigate the effect of PG-APS on human neutrophil (polymorphonuclear leukocyte [PMN]) bactericidal activity.
- To determine if PG-APS interaction with PMNs contributes to inflammation.
Main Methods:
- Human neutrophils were incubated with Staphylococcus aureus in the presence of varying PG-APS concentrations.
- Bacterial killing, PMN metabolism, and bacterial attachment to PMNs were assessed.
- Experiments were conducted with and without normal serum or heat-inactivated serum.
Main Results:
- PG-APS concentrations above 10 micrograms/ml inhibited PMN bactericidal activity against S. aureus.
- This inhibition was not due to PMN cytotoxicity or impaired oxygen metabolism.
- PG-APS (≥10 micrograms/ml) significantly reduced bacterial attachment to PMNs by 49% in the presence of normal serum.
- Inhibition of bacterial uptake correlated with reduced bactericidal activity.
- The inhibitory effect was abolished in serum-free or heat-inactivated serum conditions.
Conclusions:
- PG-APS inhibits human neutrophil-mediated killing of S. aureus.
- The mechanism involves interference with bacterial uptake, dependent on complement in normal serum.
- These findings suggest PG-APS interaction with serum components impairs PMN function, potentially contributing to inflammation.