Cuprophane haemodialysis induces upregulation of LPS receptor (CD14) on monocytes: role of complement activation

Marchant, Arnaud; Tielemans, Christian; Husson, Cécile; Gastaldello, Karine; Schurmans, Thierry; Groote, Didier De; Duchow, J.; Vanherweghem, Jean‐Louis; Goldman, Michel

doi:10.1093/oxfordjournals.ndt.a027355

Cited by 23 publications

(11 citation statements)

References 30 publications

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“…691 Earlier-generation dialyzer membranes composed of cuprophane or unmodified cellulose were more bioincompatible and had the potential to cause a “dialyzer membrane reaction”, mediated by complement activation, release of proinflammatory markers, and oxidative stress, and manifested clinically by acute hypotension, vasodilatation, leucopenia, hypoxia and fever. 692, 693, 694, 695, 696, 697 More recently, modified cellulosic membranes (with substitution of the hydroxyl groups) and synthetic membranes composed of polyacylnitrile, polysulfone, or poly(methyl methacrylate) have been developed. These “biocompatible membranes” (or less bioincompatible membranes) produce less complement and cytokine activation, and decrease oxidative stress.…”

Section: Rationalementioning

confidence: 99%

Section 5: Dialysis Interventions for Treatment of AKI

2012

Kidney International Supplements

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Section: Rationalementioning

confidence: 99%

Section 5: Dialysis Interventions for Treatment of AKI

2012

Kidney International Supplements

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“…In line with previous studies, both types of dialysers induced a similar upregulation of CD14 in PBMC at t 180 [30, 31], whereas eluted monocytes showed comparable changes. Apart from complement activation [24, 32], exposure to complexes of lipopolysaccharides (LPS) and LPS-binding protein (LBP) may be involved in the upregulation of CD14 [33]. In addition, binding of LPS-LBP complexes to CD14 may trigger cytokine release [33, 34].…”

Section: Discussionmentioning

confidence: 99%

Monocyte Activation in Peripheral Blood and Dialyser Eluates: Phenotypic Profile and Cytokine Release

Schouten

Grooteman²,

Schoorl

et al. 2002

Nephron

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Background/Aims: Monocyte activation and subsequent cytokine generation is presumed to be involved in haemodialysis (HD)-related morbidity. The present study was designed to investigate HD-induced changes in monocytes, with respect to their phenotypic profile and cytokine release, both in peripheral blood (PB) and dialyser eluates (DE). In addition, the effect of the type of dialyser on monocyte activation was assessed. Methods: Dialyser elution was performed in 8 patients after 3 h of HD, using cuprammonium (CU) and polysulfon (PS) dialysers in a randomised cross-over design. PB samples and DE were analysed for both the expression of a variety of monocyte cell surface markers (CD62L, CD11b, CD25, HLA-DR, CD64 and CD14) by flow cytometry and IL-1β levels. Monocytes were identified by dual labelling with antibodies against CD14. Results: In PB, the expression of CD11b increased during HD with both devices, but was more pronounced with CU (CU versus PS: p < 0.05). CD62L decreased during HD, but only significantly for PS (p < 0.02). HLA-DR was downregulated during HD with CU (p = 0.056). The expression of CD64 was higher during HD with CU (p = 0.02). Finally, CD14 increased during HD with both dialysers (p < 0.03). DE yielded a mean cell count of 51 × 10⁶ cells. The proportion of monocytes in DE was 3% for CU and 4% for PS. In eluted monocytes, a significant upregulation of CD11b, CD25, and HLA-DR was observed. CD62L was downregulated when compared to PB at t₁₈₀ (p < 0.001). In DE, no correlation was found between the type of dialyser and the phenotypic changes. In 10 of 16 DE supernatants, 6 CU and 4 PS, IL-1β release could be demonstrated, CU yielding significantly more of this cytokine than PS (p = 0.03). Conclusions: According to both their phenotypic profile and cytokine release, monocytes sticking to the dialyser membrane after HD are considerably more activated than circulating monocytes. Activation of eluted monocytes appeared independent of the type of dialyser, suggesting an effect of mechanical stress rather than bioincompatibility. In contrast, phenotypic activation of peripheral blood monocytes and cytokine release in the DE supernatant were mainly dialyser-dependent.

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“…To our knowledge, however, for the detection of LAL-negative pyrogens such as low-molecular-weight fragment of LPS a bioassay is needed to determine monocyte activation such as the production and release of cytokines from monocytes during treatment [25, 31]. We consider that this study was also a bioassay, since changes in Mac-1 and CD14 expression on monocytes and serum CD14 level may be considered as markers of monocyte activation [1, 2, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18]. Also, our study revealed no significant difference in the monocyte Mac-1 and CD14 expression and the serum sCD14 level between PS membrane hemodialysis and PS membrane push/pull HDF, during which the body fluid replacement volume for the first 180 min of the treatment was 42.7 ± 1.9 liters.…”

Section: Discussionmentioning

confidence: 99%

“…When LPS-LBP complex binds to CD14 on monocytes, Toll-like receptor mediates lipopolysaccharide-induced cellular signaling, resulting in monocyte activation [8]. When monocytes are stimulated by LPS, activated complement products or several cytokines such as interleukin-4 (IL-4), IL-1 and TNF, the expression of CD14 is also reported to alter [9, 10, 11, 12, 13, 14]and to be released (shed) from the cell surface of monocytes in a soluble form, resulting in the elevation of the serum soluble CD14 (sCD14) concentration [15, 16, 17, 18]. Taking these reports into consideration, Mac-1 and CD14 expressions on monocyte and serum sCD14 level may be considered as markers of monocyte activation.…”

Section: Introductionmentioning

confidence: 99%

Changes in Mac-1 and CD14 Expression on Monocytes and Serum Soluble CD14 Level during Push/Pull Hemodiafiltration

Kono¹,

Nakai²,

Misawa³

et al. 2002

Nephron

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Background/Aim: Employment of treated dialysate as replacement fluid raises concerns about exposure of patients to pyrogenic substances. This study was undertaken to evaluate the safety of treated dialysate as the replacement fluid for push/pull hemodiafiltration. Methods: In the present study, changes in the expressions of Mac-1 and CD14 on monocytes, which are upregulated by monocyte activation, were analyzed by flow cytometry, and the serum level of sCD14 which elevates by monocyte activation was measured by enzyme-linked immunosorbent assay (ELISA) during treatment in 7 patients on hemodialysis with regenerated cellulose (RC) membrane, polysulfone (PS) membranes and by push/pull hemodiafiltration (HDF) with PS membranes in a cross-over fashion. Results: During hemodialysis with RC, hemodialysis with PS or push/pull hemodiafiltration with PS, both Mac-1 and CD14 expressions on monocytes significantly increased by passing through the artificial kidneys, and, accordingly, the respective values downstream of the artificial kidneys were significantly higher than the predialysis values, even when the lipopolysaccharide level in dialysate was not detectable by Limulus assay. There was no significant variation in serum sCD14 levels during any of the hemodialysis with RC, hemodialysis with PS or push/pull hemodiafiltration. However, during hemodialysis with PS or push/pull hemodiafiltration with PS, changes in Mac-1 and CD14 expression on monocytes were significantly smaller than those during hemodialysis with RC. Conclusion: Monocytes are activated to a greater extent during hemodialysis with RC membranes than during push/pull HDF with PS membranes. We consider that push/pull HDF may be safer than hemodialysis with RC membrane and that it is as safe as hemodialysis with the PS membrane in terms of monocyte activation, when pyrogen-free dialysate is employed.

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Cuprophane haemodialysis induces upregulation of LPS receptor (CD14) on monocytes: role of complement activation

Abstract: Haemodialysis on the complement-activating cuprophane membrane induces the rapid upregulation of the CD14 LPS-receptor on monocytes.

Cited by 23 publications

References 30 publications

Section 5: Dialysis Interventions for Treatment of AKI

Section 5: Dialysis Interventions for Treatment of AKI

Monocyte Activation in Peripheral Blood and Dialyser Eluates: Phenotypic Profile and Cytokine Release

Changes in Mac-1 and CD14 Expression on Monocytes and Serum Soluble CD14 Level during Push/Pull Hemodiafiltration

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