Apoptosis of monocytes cultured from long-term hemodialysis patients.
Monocyte apoptosis in vitro was studied in patients on long-term hemodialysis, CAPD, and in predialytic uremia to gain insight into the high susceptibility of these patients to infections. Monocytes from dialysis and control subjects were cultured for 24 to 120 hours in vitro to analyze the level and progression of DNA fragmentation as a hallmark of apoptosis. After an incubation time of 48 hours chromatin fragmentation of 48.5 +/- 7.7% was found in monocytes from dialysis patients, which significantly exceeded DNA fragmentation of control monocytes (23.1 +/- 9.1%; N = 12; P 95% both in the dialysis and control group. Hemodialysis patients also showed elevated levels of monocyte apoptosis when programmed cell death was evaluated by transmission electron microscopy or DNA electrophoresis of cleaved chromatin. To test the functional relevance of monocyte apoptosis, a significant reduction of Candida growth inhibition by monocytes of dialysis patients was found with a strong linkage between percentage of DNA fragmentation and impaired microbicidal capacity. Monocytes obtained from patients after the hemodialysis session and from CAPD patients showed normal DNA fragmentation levels similar to controls. Differences of monocyte apoptosis between patients on cuprophane and high-flux polysulphone dialysis were not found. Uremic predialytic patients also exerted an increased monocyte DNA fragmentation of 44.2 +/- 1.5% (N = 7; P
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