Anticoagulation-Dependent Inhibition of in vitro Complement Activation by Anti-Apo-B Sepharose 4B CL

Kadar, J; Parusel, M.; Borberg, H.

doi:10.1159/000222635

Cited by 3 publications

(2 citation statements)

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“…Combined heparin-ACD-A anti-coagulation was used in these preclinical feasibility studies for several reasons. First, this anti-coagulant combination has been shown to minimize complement activation during clinical LDL-apheresis [39,40]. Secondly, ACD-A decreases platelet and granulocyte aggregation [41].…”

Section: Discussionmentioning

confidence: 99%

Exploring the feasibility of selective depletion of T lymphocyte subsets by whole blood immunoadsorption cytapheresis

Belák¹,

Valeri

Wright³

2007

Clinical and Experimental Immunology

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SummaryNormal turnover of T lymphocytes is slow relative to other blood cells. Consequently, the physical removal of circulating leucocytes by thoracic duct drainage, repeated leukapheresis or blood filtration results in T cell depletion and immunosuppression. However, clinical use of such procedures is impractical compared with immunosuppressive drugs or radiation. None the less, immunosuppression by physical depletion of T cells, avoiding the systemic toxicities of drugs and radiation, might have clinical advantages if immunophenotypically distinct T cell subsets could be depleted selectively. Recent advances in targeted plasma protein apheresis using adsorbent macrobead columns prompted us to determine whether analogous techniques might permit CD4+ T lymphocytes to be removed selectively from whole blood. To explore this possibility, we linked murine anti-human-CD4 and isotypeidentical control monoclonal antibodies (mAbs) to agarose, polyacrylamide and polystyrene macrobeads (150-350 mm) and then evaluated the selectivity, specificity and efficiency of macrobead columns to remove CD4 + T cells from anti-coagulated whole blood at varying mAb densities and flow rates. We also examined saturation kinetics and Fc-oriention versus random coupling of mAbs to macrobeads. Sepharose 6MB macrobead (250-350 mm) columns proved to be most effective, selectively removing up to 98% of CD4 + T cells from whole blood. Moreover, depletion efficiency and selectivity were retained when these columns were reused after elution of adherent CD4 + cells. These studies indicate that selective depletion of T lymphocyte subsets by whole blood immunoadsorption apheresis using mAb-linked macrobead columns may be feasible on a clinical scale. It is possible that such apheresis techniques could achieve targeted forms of immunosuppression not possible with drugs or radiation.

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Section: Discussionmentioning

confidence: 99%

Exploring the feasibility of selective depletion of T lymphocyte subsets by whole blood immunoadsorption cytapheresis

Belák¹,

Valeri

Wright³

2007

Clinical and Experimental Immunology

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“…Ethylenediaminetetraacetic acid (EDTA) and sodium citrate are calcium chelators in clinical use, citrate being a standard anticoagulant in hemodialysis (13,14) and blood transfusion. There are data showing significant inhibition of the complement system (15) in the citrate concentration range used to obtain anticoagulation, although complement inhibition is not total (16,17). Calcium chelation also has the potential to block inflammatory cells such as mast cells (18).…”

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confidence: 99%

Substituting Citrate for Lactate in Peritoneal Dialysis Fluid Improves Ultrafiltration in Rats

2009

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Background Exposure to peritoneal dialysis (PD) fluid induces an inflammatory response in the peritoneal cavity. Blockers of complement and coagulation have improved ultrafiltration in animal models of PD. Citrate is a clinically established anticoagulant that also blocks complement activation. Objective The aim of the present study was to evaluate the effects on ultrafiltration of a gradual substitution of citrate for lactate in an experimental model of PD. Methods Fractions (0, 5, 10, and 15 mmol/L) of the 40 mmol/L lactate buffer of filter-sterilized 2.5% glucose PD fluid were replaced by citrate. The modified fluids were compared in a rat model of single PD fluid exposure through an indwelling catheter. The initial kinetics of citrate and ionized calcium were evaluated in separate, single, short time dwell experiments. Results Replacing 10 and 15 mmol/L of the lactate buffer by sodium citrate significantly increased osmotic ultrafiltration (by 24.7% ± 7.7% at 10 mmol/L), net ultrafiltration, and glucose retention at 4 hours of dwell time in the rat model. Osmotic ultrafiltration was significantly correlated to citrate concentration and glucose concentration. Citrate was rapidly eliminated from the peritoneal cavity, concentrations falling to less than half in 1 hour and concentrations of calcium ions concomitantly normalized. Conclusions Substituting citrate for lactate induced a dose-dependent increase in ultrafiltration. Mechanisms probably involve the relation between diffusion and ultrafiltration, leading to increased glucose retention. The increase in ultrafiltration was quantitatively important at a citrate concentration (10 mmol/L) that is compatible with clinical applications of citrate.

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Detection of surface bound complement at increasing serum anticoagulant concentrations

Arvidsson

Askendal

Lindahl³

et al. 2008

Colloids and Surfaces B: Biointerfaces

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Anticoagulation-Dependent Inhibition of in vitro Complement Activation by Anti-Apo-B Sepharose 4B CL

Cited by 3 publications

References 0 publications

Exploring the feasibility of selective depletion of T lymphocyte subsets by whole blood immunoadsorption cytapheresis

Exploring the feasibility of selective depletion of T lymphocyte subsets by whole blood immunoadsorption cytapheresis

Substituting Citrate for Lactate in Peritoneal Dialysis Fluid Improves Ultrafiltration in Rats

Detection of surface bound complement at increasing serum anticoagulant concentrations

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