C3a and C5a Anaphylatoxins Bind to Heparin‐Based Sorbent in Low Density Lipoprotein Apheresis: In Vitro and In Vivo Investigations

Abstract

Plasmasorption on a heparin-based sorbent was performed in vitro. It demonstrated affinity of the C3a and C5a anaphylatoxins for the sorbent: C3a was removed almost completely (97%), and the C5a concentration decreased on average by 55%. The plasma level of C3a and C5a complement components was also monitored during the procedure of clinical extracorporeal low density lipoprotein (LDL) apheresis on the sorbent in patients with familial hypercholesterolemia. A two- to threefold increase in C3a (up to 1,500 ng/ml) was observed after plasma separation by the IBM 2997 cell sorter. Subsequent processing of the plasma through the column led to the low level of C3a detected (less than 50 ng/ml), demonstrating significant uptake of C3a by the sorbent column. The removed C3a was found in the eluate obtained after regeneration of the sorbent with 2 M NaCl solution. No significant increase in C5a was found during the procedure. Nevertheless, some C5a was detected in the eluate from the sorbent. The content of C3a and C5a in patients blood after the treatment was approximately the same as it was initially, 200-500 ng/ml for C3a and less than 10 ng/ml for C5a. The removal of C3a and C5a anaphylatoxins by heparin-based sorbent should be regarded as an advantage of this type of plasmasorbent.

In vitro evaluation of heparinized Cuprophan hemodialysis membranes

“…4,[41][42][43] It has even been reported that in certain cases immobilized heparin has a high affinity for binding C3a. 41,44 Deppisch et al 39 showed that TCC does not readily adsorb onto biomaterials. For heparinized materials, however, adsorption of TCC has not been investigated in detail, although Pekna et al, 45 who studied complement activation by poly(methyl methacrylate) and heparinized poly(methyl methacrylate), showed that total C3 activation and fluid phase TCC generation correlated well.…”

Hemocompatibility of Silicon-Based Substrates for Biomedical Implant Applications

“…At high concentrations, heparin binds heparin cofactor II to inhibit thrombin independent of antithrombin; however, it also binds to platelets and induces their aggregation. Heparin also binds anaphylotoxins such as the complement protein C3a 30. Sodium citrate neutralizes coagulation factor activation.…”

Synthetic di-sulfated iduronic acid attenuates asthmatic response by blocking T-cell recruitment to inflammatory sites

“…To next study the specificity of Di-S-IdoA, the inhibitory effect of Di-S-IdoA on the bindings between the various proteins and endothelial cells was assayed. It is known that CCL21 (23, 24), IL-8 (23, 25), L-selectin (26,27), and complement component 5a (C5a) (28,29) are involved both in the binding to heparin/heparan sulfate in vitro and in the asthma pathogenesis. The result showed that Di-S-IdoA did not block the attachment of CCL21 to mouse endothelial F2 cells, whereas heparin efficiently blocked ( (Fig.…”