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Suppressor resident peritoneal macrophages and peritonitis incidence in continuous ambulatory peritoneal dialysis
Abstract:
Our study was designed to see if peritoneal macrophages (PM) of continuous ambulatory peritoneal dialysis (CAPD) uremic patients, by weakening local defense, could contribute to an increase of peritonitis incidence. Coincubation of nonadherent control responding cells (NACRC) and PM from normal subjects or CAPD patients with low peritonitis incidence (LPI) did not modify blastogenic response of cells to PHA. Coincubation of NACRC and PM from CAPD patients with high peritonitis incidence (HPI) produced noticeable decrease in blastogenic response; these PM, unable to produce normal amounts of Interleukin-1 (IL-1), released large amounts of prostaglandin E2 (PGE2). CAPD patients with LPI and normal subjects produced both substances in similar amounts. PM of CAPD patients with HPI were less able to kill bacteria than those from normal subjects and CAPD patients with LPI, showing a stronger suppressor effect on local defense. This suppressor activity correlated directly to PGE2 release and inversely to IL-1 production. We can hypothesize that in some uremic patients, subpopulations of macrophages growing in response to local stimuli produce humoral substances, negatively affecting cellular-mediated defense and favoring elevated bacterial expansion in peritoneum.
Insights
Peritoneal macrophages in continuous ambulatory peritoneal dialysis (CAPD) patients with high peritonitis incidence (HPI) show weakened defense. These macrophages release excess prostaglandin E2 (PGE2), reducing interleukin-1 (IL-1) and impairing bacterial clearance.
Area of Science:
- Immunology
- Nephrology
- Cell Biology
Background:
- Peritonitis is a common complication in continuous ambulatory peritoneal dialysis (CAPD).
- The role of peritoneal macrophages (PM) in the immune defense of CAPD patients is not fully understood.
- Understanding PM function may reveal mechanisms contributing to peritonitis incidence.
Purpose of the Study:
- To investigate the function of peritoneal macrophages (PM) in CAPD patients.
- To determine if PM dysfunction contributes to increased peritonitis incidence in CAPD.
- To explore the relationship between PM function and specific inflammatory mediators.
Main Methods:
- Coincubation of nonadherent control responding cells (NACRC) with PM from normal subjects and CAPD patients (low and high peritonitis incidence).
- Assessment of blastogenic response to PHA (phytohemagglutinin) as a measure of cellular immune response.
- Quantification of Interleukin-1 (IL-1) and prostaglandin E2 (PGE2) production by PM.
- Evaluation of bacterial killing capacity of PM.
Main Results:
- PM from CAPD patients with high peritonitis incidence (HPI) showed decreased blastogenic response of NACRC.
- These HPI-PM produced less Interleukin-1 (IL-1) and significantly more prostaglandin E2 (PGE2) compared to controls.
- PM from HPI patients exhibited reduced bacterial killing ability and a stronger suppressor effect on local defense.
- Suppressor activity correlated positively with PGE2 release and negatively with IL-1 production.
Conclusions:
- Peritoneal macrophages in some CAPD patients with high peritonitis incidence exhibit impaired function.
- Increased prostaglandin E2 (PGE2) production and reduced Interleukin-1 (IL-1) by these macrophages may weaken local peritoneal defense.
- This dysfunction likely contributes to increased susceptibility to bacterial infections and peritonitis in CAPD patients.