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Peritoneal defence mechanisms and Staphylococcus aureus in patients treated with continuous ambulatory peritoneal
S J Davies1, V M Yewdall, C S Ogg
1Renal Unit, Guy's Hospital, London, United Kingdom.
Abstract:
Peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients due to S. aureus is associated with an adverse clinical outcome, suggesting impaired clearance of this organism by the host. The ability of peritoneal macrophages (PM0) derived from CAPD patients to take up S. aureus and mount a respiratory burst was investigated. Whilst significant activity was observed in the absence of opsonin, both parameters of phagocytosis were augmented by addition of 20% pooled human serum (PHS), complement-depleted PHS, and fibronectin. When used as sole opsonin, fibronectin resulted in a dose-related increase in chemiluminescent response by both blood neutrophils and PM0. The opsonic activity of dialysis effluent, as judged by neutrophil chemiluminescence, correlated with IgG and fibronectin content, but not with complement as assessed by C3 levels. The addition of urokinase to dialysate improved its opsonic properties whilst having no effect on the activity of PHS-20%; this would suggest that the formation of fibrin in dialysate, promoted by S. aureus, interferes with phagocytosis. This and the low IgG, complement and fibronectin levels in dialysate may explain in part the relatively poor clearance of this organism from the peritoneum.
Insights
Staphylococcus aureus peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients may stem from impaired macrophage function. Dialysis fluid composition, particularly low immunoglobulin G (IgG) and fibronectin, hinders bacterial clearance.
Area of Science:
- Immunology
- Nephrology
- Microbiology
Background:
- Peritonitis caused by Staphylococcus aureus in continuous ambulatory peritoneal dialysis (CAPD) patients is linked to poor clinical outcomes.
- This suggests a potential impairment in the host's ability to clear S. aureus from the peritoneal cavity.
Purpose of the Study:
- To investigate the phagocytic capacity of peritoneal macrophages (PMNs) from CAPD patients against S. aureus.
- To assess the role of opsonins like pooled human serum (PHS), complement, and fibronectin in S. aureus uptake and respiratory burst activity.
Main Methods:
- Peritoneal macrophages (PMNs) were isolated from CAPD patients.
- Phagocytosis and respiratory burst assays were performed using S. aureus, with and without various opsonins (PHS, complement-depleted PHS, fibronectin).
- Neutrophil chemiluminescence was used to evaluate the opsonic activity of dialysis effluent, correlating it with IgG, fibronectin, and C3 complement levels.
Main Results:
- PMNs from CAPD patients showed phagocytic activity against S. aureus, which was enhanced by PHS, complement-depleted PHS, and fibronectin.
- Fibronectin acted as a potent opsonin, dose-dependently increasing chemiluminescence in both blood neutrophils and PMNs.
- Dialysis effluent opsonic activity correlated with IgG and fibronectin, but not C3 levels. Urokinase improved opsonic properties, suggesting fibrin interferes with phagocytosis.
Conclusions:
- Impaired phagocytosis by peritoneal macrophages may contribute to adverse outcomes in CAPD patients with S. aureus peritonitis.
- Low levels of IgG, complement, and fibronectin in dialysis fluid, along with potential fibrin formation, likely hinder S. aureus clearance from the peritoneum.