Increased protein loss during peritonitis associated with peritoneal dialysis is neutrophil dependent

Background. Peritonitis in peritoneal dialysis patients is accompanied by a n enhanced migration of neutrophils (PMNs) and increased protein loss into the peritoneal cavity; however. the role of PMNs in governing increased pro tein loss during peritonitis associated with peritoneal dialysis is unknown . Methods. We determined the importance of PMNs in governing changes in perit oneal permeability to protein in New Zealand White rabbits in which acute p eritonitis was induced by adding 4 x 10(6) colony-forming units of Escheric hia coli to 35 mL/kg of 0.9% saline dialysate. The total leukocyte and PMN migration into the peritoneal cavity was assessed by differential cell coun ts in the dialysate, and peritoneal permeability to protein was evaluated b y calculating the dialysate to plasma concentration ratio for total protein as a function of time during a six- or eight-hour dwell. In series 1 exper iments, leukocytes were depleted from the rabbit circulation by an intraven ous injection of mustine (1.2 mg/kg) three days before the experiment; in s eries 2 experiments, integrin-dependent PMN migration into the peritoneal c avity was inhibited by an intravenous injection of monoclonal antibody (mAb ) 60.3 (2 mg/kg) directed against the integrin CD18 on leukocytes five minu tes before the experiment. Results. In series 1 experiments, mustine decreased circulating leukocytes by 82 +/- 5% (mean +/- SEM) and circulating PMNs by 93 +/- 3%. Total leukoc yte and PMN migration into the peritoneal cavity and peritoneal permeabilit y to protein were decreased in mustine-treated rabbits after exposure to E. coli in the dialysate to levels similar to those found in rabbits without bacterial peritonitis. In series 2 experiments, an intravenous injection of anti-CD18 antibody also abrogated both the enhanced PMN migration into the peritoneal cavity and the increased peritoneal permeability to protein aft er exposure to E. coli in the dialysate. Conclusions. PMN migration into the peritoneal cavity is integrin dependent . Increased protein loss during acute, gram-negative bacterial peritonitis in a rabbit model of peritoneal dialysis is PMN dependent.