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Interaction of group A streptococcal peptidoglycan polysaccharide with human polymorphonuclear leukocytes:
Abstract:
Injection of sterile aqueous preparations of the peptidoglycan polysaccharide of group A streptococci produces chronic inflammation in several animal models. Accordingly, the effect of peptidoglycan and group A-specific polysaccharide (PG-APS) polymers on human polymorphonuclear neutrophil oxidative metabolism was studied with the supposition that this interaction may contribute to the inflammation observed. PG-APS in concentrations of 1.0 to 100 micrograms/ml stimulated oxygen consumption and hexose monophosphate shunt activity in the presence of 10% normal serum in a dose-related manner. Stimulation did not occur in serum-free media and was reduced in media with heat-treated serum. The stimulation of hexose monophosphate shunt activity by PG-APS opsonized with normal serum (bound complement components) and the activated supernatant from which PG-APS had been removed by centrifugation (presumably containing the soluble complement component, C5a) demonstrated 79 and 75%, respectively, of the stimulation with PG-APS in the presence of 10% normal serum. PG-APS triggered release of O2- (3.4 +/- 2.0 nmol by 10(6) human polymorphonuclear neutrophils over 30 min), which was significantly enhanced (9.6 +/- 2.9 nmol O2-) by treatment of cells with cytochalasin B. These results show that PG-APS interacts with serum in such a fashion as to activate human polymorphonuclear neutrophil metabolism and increase secretion of O2-.
Insights
Group A streptococcal peptidoglycan polysaccharide (PG-APS) activates human immune cells. This interaction with serum components stimulates neutrophils, increasing oxygen consumption and superoxide release, potentially contributing to inflammation.
Area of Science:
- Immunology
- Microbiology
Background:
- Peptidoglycan polysaccharide (PG-APS) from group A streptococci induces chronic inflammation in animal models.
- The mechanism by which PG-APS contributes to inflammation is not fully understood.
Purpose of the Study:
- To investigate the effect of PG-APS on human polymorphonuclear neutrophil (PMN) oxidative metabolism.
- To determine if PG-APS interaction with serum components mediates PMN activation.
Main Methods:
- Human PMNs were incubated with varying concentrations of PG-APS in the presence of normal or heat-treated serum.
- Oxygen consumption and hexose monophosphate shunt activity were measured.
- Superoxide anion (O2-) release was quantified, with and without cytochalasin B treatment.
Main Results:
- PG-APS stimulated PMN oxygen consumption and hexose monophosphate shunt activity in a dose-dependent manner, requiring serum.
- Complement components (bound and soluble C5a) in serum were crucial for PG-APS-mediated PMN activation.
- PG-APS triggered significant O2- release from PMNs, further enhanced by cytochalasin B.
Conclusions:
- PG-APS interacts with serum components to activate human PMN oxidative metabolism.
- This activation leads to increased superoxide secretion, suggesting a role in streptococcal-induced inflammation.