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

Abstract

.IntroductionThe 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 MethodsThe 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 × min). The expressions of CD11b/CD18, CD10, and CD13 receptors were determined with flow cytometry.ResultsBasal PMN CL was increased in HD patients to up to 1285 ± 129 aU × min compared with 895 ± 88 aU × min in healthy controls (p < 0.05). The CL of unprimed PMNs increased after fMLP stimulation from 3085 ± 746 to 4529 ± 808 aU × min, and after OZ stimulation from 12945 ± 1296 to 14678 ± 1355 aU × 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-α alone. The CL of TNF-α-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 β-integrin heterodimer compound, CD18, was not increased.ConclusionsThese results provide evidence that TNF-α priming of PMNs is down-regulated in HD patients despite constitutive up-regulation of resting cytotoxicity and enhanced expression of adhesion and metalloproteinase receptors.