TNF-alpha priming effect on polymorphonuclear leukocyte reactive oxygen species generation and adhesion molecule expression in hemodialyzed patients.

INTRODUCTION: The study aimed to assess reactive oxygen species generation and the expressions of some surface antigens on polymorphonuclear leukocytes (PMNs) in patients on regular hemodialysis (HD) treatment.
MATERIALS AND METHODS: The respiratory burst of PMNs was determined with luminol-dependent chemiluminescence (CL) in resting cells and following N-formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol 12-myristate 13-acetate (PMA), or opsonized zymosan (OZ) stimulation and expressed in arbitrary CL units times assay-time (aU x min). The expressions of CD11b/CD18, CD10, and CD13 receptors were determined with flow cytometry.
RESULTS: Basal PMN CL was increased in HD patients to up to 1285 +/- 129 aU x min compared with 895 +/- 88 aU x min in healthy controls (p < 0.05). The CL of unprimed PMNs increased after fMLP stimulation from 3085 +/- 746 to 4529 +/- 808 aU x min, and after OZ stimulation from 12945 +/- 1296 to 14678 +/- 1355 aU x min. PMA-stimulated CL of PMNs was similar to control values. The oxidative burst in PMNs from HD patients and healthy controls was similar in response to TNF-alpha alone. The CL of TNF-alpha-primed PMNs in HD patients was significantly lower than CL measured in healthy controls (p < 0.05). The expressions of CD10 and CD13 metalloproteinase receptors were also increased (p < 0.05). Although CD11b expression was significantly increased at rest and after fMLP stimulation, the expression of another beta-integrin heterodimer compound, CD18, was not increased.
CONCLUSIONS: These results provide evidence that TNF-alpha priming of PMNs is down-regulated in HD patients despite constitutive up-regulation of resting cytotoxicity and enhanced expression of adhesion and metalloproteinase receptors.