title: Effect of dialyser membranes on extracellular and intracellular granulocyte and monocyte activation in ex vivo pyrogen-free conditions.
abstract: This study examined effects of blood-contacting materials on the monocyte reaction following the first contact of human blood with hollow fibre dialyser membranes under pyrogen-free conditions. Membrane materials were the unchanged regenerated cellulose, the synthetic polysulphone (PS), a positively charged diethylaminoethyl cellulose (DEAE-C), the negatively charged carboxymethyl cellulose (CMC) and acrylonitrile copolymer (AN). The experimental system involved perfusion with human fresh venous blood through different modules containing the materials in the form of hollow fibre membranes. Extracellular and intracellular aspects of blood reactions after the first contact with the materials were investigated in Ficoll-separated granulocytes and peripheral blood mononuclear cells. Investigations were done by release reactions of platelet activating factor (PAF), oxygen radical (O2-), leukotriene B4, prostaglandin E2 (PGE2) and cytokines (IL-1 beta, TNF-alpha, IL-6). The intracellular activation of peripheral blood mononuclear cells was done by mRNA transcription of IL-1 beta, TNF-alpha, IL-6, IL-8 and beta 2-microglobulin (beta 2-MG). From the set of parameters, release reactions were only measurable for PAF, PGE2 and O2- if a second stimulus (phorbol myristate acetate, lipopolysaccharide, zymosan and calcium ionophore) was used after blood-membrane interaction. Although the extent of the release reaction was weak, negatively charged membranes were, in general, more active. All dialysers exhibited the same increase in beta 2-MG mRNA transcription, suggesting that all blood-contacting membranes initiate the gene expression of beta 2-MG at the same level. TNF-alpha, IL-6, IL-1 beta and IL-8 mRNAs were demonstrated in the AN and CMC membranes rather than the other materials, which exhibit a lower transcription than the tubing set. As has been found, an enhanced generation of PGE2 for both CMC and AN membranes supports, therefore, the concept of an effect of the negative charges of the materials in the gene expression of cytokines. However, this initiation does not lead to the generation of cytokines, even after stimulation with pyrogens.
authors.affiliation: Medical School Hanover, Department of Nephrology, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Mahiout
authors.forename: J M
authors.initials: JM
authors.lastname: Courtney
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D016207:Cytokines / Q000494:pharmacology*; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D008422:Materials Testing; D008567:Membranes, Artificial; D009000:Monocytes / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000302:isolation & purification; D011817:Rabbits; D006435:Renal Dialysis; D013481:Superoxides / Q000302:isolation & purification / Q000378:metabolism; D014158:Transcription, Genetic; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D008567:Membranes, Artificial; D001613:beta 2-Microglobulin; D013481:Superoxides; D007975:Leukotriene B4; D012313:RNA