Rate of clearance by the spleen of heat-damaged erythrocytes.

Red blood cells (RBCs) attract significant interest as carriers of biomolecules, drugs and nanoparticles. In this regard, versatile technologies to attach molecules and ligands to the RBC surface are of great importance. Reported here is a fast and efficient surface painting strategy to attach ligands to the surface of RBCs, and the factors that control the stability and circulation properties of the modified RBCs in vivo. Distearoyl phosphatidylethanolamine anchor-conjugated immunoglobulin (IgG) efficiently incorporates in the RBC membrane following 15–30 min incubation. The optimized RBCs show prolonged circulation in vivo (70% of the injected dose after 48h) and efficient retention of IgG in the membrane with terminal half-life of 73 hours. The IgG construct is gradually lost from the RBCs mainly due to the transfer to plasma components, liver endothelial cells and Kupffer cells. The ligand retention efficiency is partially dictated by ligand type, anchor type, and ligand concentration in the membrane, while RBC half-life is determined by initial concentration of the ligand in the membrane and presence of PEG linker between the ligand and the anchor. This work provides important guidance for non-covalent surface painting of RBCs as well as other types of blood borne cells for in vivo therapeutic and targeting applications.

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“…Damaged RBCs are rapidly sequestered by the immune system, mostly Kupffer macrophages and marginal zone macrophages in the spleen. [6] …”

Section: Introductionmentioning

confidence: 99%

Distearoyl Anchor‐Painted Erythrocytes with Prolonged Ligand Retention and Circulation Properties In Vivo

Shi¹,

Mukthavaram²,

Kesari³

et al. 2013

Adv Healthcare Materials

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“…Thus, injection of aqueous hemin would preferentially stimulate liver, specifically hepatocyte, HO activity. In contrast, heat-damaged RBC are cleared from the circulation by the macrophages of the RES, particularly those in the spleen (20). A similar mechanism is responsible for clearing damaged RBC from the circulation of the neonate with hemolytic disease (1).…”

Section: Resultsmentioning

confidence: 99%

Targeting Zinc Protoporphyrin Liposomes to the Spleen Using Reticuloendothelial Blockade with Blank Liposomes

et al. 1993

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“…Apotential problem of the determination of the clearance of the heat-alterederythrocytesisthe fact thatthe spleen mayalready have eliminatedaconsiderablep arto ft he heat-alterede rythrocytesf rom the blood when the firstbloodsample is taken after3 minutesl eading to an underestimation of the 100% value (4,10).This could meanthat patients in the so-calledgreyzone mayhave normal splenic function.H owever,i ti s necessaryt ow aitf or 2-3 minutes afteri njection before taking the firstbloodsample to allowt he radiolabeled erythrocytes to evenly distribute in the blood. Theuse of the clearance of heat-alterede rythrocytesa s standard technique for the determination of splenic function maya lsob eh amperedb y the fact thatr adioactivef ragments of erythrocytes aret aken up by the RESi nt he liver.…”

Section: Discussionmentioning

confidence: 99%

Scintigraphy with 99mTc-labeled heat-altered erythrocytes in diagnosing hyposplenia

Gotthardt¹,

Bröker²,

Schlieck³

et al. 2007

Nuklearmedizin

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Summary Aim: Ultrasound may be a cheap alternative to scintigraphic determination of splenic function. We directly compared nanocolloid scintigraphy (NS), scintigraphy with heat-altered erythrocytes (ES), and colour-coded Doppler sonography (DS) in patients with chronic inflammatory bowel disease (CIBD). Patients, methods: 35 patients were included into the study. Clearance rates were determined in ES, spleen/liver ratios (SLR) were measured scintigraphically in ES/NS. In DS, spleen size, echogenicity, and vascular resistance indices (RI) were determined. The results were compared to each other, to the clinical activity scores for CIBD, and to the course of the disease. Results: Based on the blood erythrocyte clearance serving as standard, patients had a good (19 patients), impaired (5), or missing splenic function (11). There was a good correlation of the clearance to SLR in ES (0.63, p <0.01). The 10 min / 45 min ES clearance showed a high correlation (Spearman- Rho 0.87, p <0.01). The SLR in ES at 2, 5, 10 and 45 min also correlated well with each other (Spearman- Rho >0.9, p <0.01; SLR >3.45 normal splenic function, SLR <1.22 indicated hyposplenia). There were no correlations between the results of NS, DS, Howell-Jollybodies, or clinical parameters. Only ES and the erythrocyte clearance correlated well. Howell-Jolly-Bodies detected 1 of 11 patients with hyposplenia while false-positive in 4. Conclusion: Ultrasound and colloid scintigraphy show a low correlation with clearance of heat-altered erythrocytes. Only ES shows a good correlation in patients with CIBD. The clearance at 10 min already reliably determines splenic function. SLR may be determined after 10 minutes and is predictive of normal function if above 3.45 while SLR <1.2 indicated hyposplenia.

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Rate of clearance by the spleen of heat-damaged erythrocytes.

Cited by 26 publications

References 6 publications

Distearoyl Anchor‐Painted Erythrocytes with Prolonged Ligand Retention and Circulation Properties In Vivo

Distearoyl Anchor‐Painted Erythrocytes with Prolonged Ligand Retention and Circulation Properties In Vivo

Targeting Zinc Protoporphyrin Liposomes to the Spleen Using Reticuloendothelial Blockade with Blank Liposomes

Scintigraphy with 99mTc-labeled heat-altered erythrocytes in diagnosing hyposplenia

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