Effects of conventional peritoneal dialysates on leukocyte adhesion and CD11b, CD18 and CD14 expression

Abstract

Bacterial peritonitis is the most important complication of peritoneal dialysis (PD), limiting its widespread application. Conventional glucose-based peritoneal dialysates (G-PDS) depress oxygen consumption, chemiluminescence, superoxide production, phagocytosis, bacterial killing and actin polymerization in neutrophils (PMN) in vitro. Expression of adhesion receptors is critical to leukocyte activation, adhesion, migration and phagocytosis. The effects of G-PDS on basal and stimulated leukocyte adhesion molecule expression and leukocyte adhering capacity is unknown. We examined the effect of a five minutes incubation of whole blood in either HEPES-buffered saline or G-PDS containing 1.5% (83 mM), 2.5% (139 mM) or 4.25% (236 mM) glucose, at pH = 5.2, and pH = 7.4. PMN intracellular pH was measured spectrofluorometrically. Leukocyte CD11b, CD18 and CD14 were measured by flow cytometry using monoclonal antibodies in otherwise unstimulated cells or 60 minutes after lipopolysaccharide (LPS) stimulation. In addition, leukocyte adhering capacity to nylon wool was tested. In an attempt to dissect the effect of high glucose concentrations from that of the attendant hyperosmolality, the experiments were repeated with dialysates in which glucose was substituted by sodium chloride (NaCl-PDS) to attain identical osmolalities. G-PDS, as well as the mixtures of spent and fresh G-PDS, significantly depressed the basal PMN expression of adhesion receptors CD11b and CD18 and monocyte expression of CD14, and substantially mitigated the LPS-mediated up-regulation of CD11b and CD18. Likewise, G-PDS significantly inhibited leukocyte adhering capacity without affecting cell viability. Similar results were observed with NaCl-PDS. The observed abnormalities were primarily osmolality-dependent, and largely intra- and extracellular pH-independent. Impaired adhesion receptor expression and cell adhesion capacity shown here reveal another dimension of the G-PDS-induced leukocyte abnormalities.