Absence of peripheral blood mononuclear cells priming in hemodialysis patients

Absence of peripheral blood mononuclear cells priming in hemodialysis patients

Author Santos, B.c. Autor UNIFESP Google Scholar
Starobinas, N. Google Scholar
Barbuto, J.a.m. Google Scholar
Russo, M. Google Scholar
Schor, Nestor Autor UNIFESP Google Scholar
Institution Universidade de São Paulo (USP)
Instituto Butantan Laboratório de Imunogenética
Universidade Federal de São Paulo (UNIFESP)
Abstract As a consequence of the proinflammatory environment occurring in dialytic patients, cytokine overproduction has been implicated in hemodialysis co-morbidity. However, there are discrepancies among the various studies that have analyzed TNF-alpha synthesis and the presence of peripheral blood mononuclear cell (PBMC) priming in this clinical setting. We measured bioactive cytokine by the L929 cell bioassay, and evaluated PBMC TNF-alpha production by 32 hemodialysis patients (HP) and 51 controls. No difference in TNF-alpha secretion was observed between controls and HP (859 ± 141 vs 697 ± 130 U/10(6) cells). Lipopolysaccharide (5 µg/ml) did not induce any further TNF-alpha release, showing no PBMC priming. Paraformaldehyde-fixed HP PBMC were not cytotoxic to L929 cells, suggesting the absence of membrane-anchored TNF-alpha. Cycloheximide inhibited PBMC cytotoxicity in HP and controls, indicating lack of a PBMC TNF-alpha pool, and dependence on de novo cytokine synthesis. Actinomycin D reduced TNF-alpha production in HP, but had no effect on controls. Therefore, our data imply that TNF-alpha production is an intrinsic activity of normal PBMC and is not altered in HP. Moreover, TNF-alpha is a product of de novo synthesis by PBMC and is not constitutively expressed on HP cell membranes. The effect of actinomycin D suggests a putative tighter control of TNF-alpha mRNA turnover in HP. This increased dependence on TNF-alpha RNA transcription in HP may reflect an adaptive response to hemodialysis stimuli.
Keywords Cytokine
Stress response
Translational control
Transcriptional blockage
Membrane-anchored tumor necrosis factor
Language English
Date 2003-02-01
Published in Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 36, n. 2, p. 219-225, 2003.
ISSN 0100-879X (Sherpa/Romeo, impact factor)
Publisher Associação Brasileira de Divulgação Científica
Extent 219-225
Origin http://dx.doi.org/10.1590/S0100-879X2003000200009
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000181135700009
SciELO ID S0100-879X2003000200009 (statistics in SciELO)
URI http://repositorio.unifesp.br/handle/11600/1656

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