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In vivo binding of circulating immune complexes by C3b receptors (CR1) of transfused erythrocytes.

The effects of packed erythrocyte transfusion with high CR1 activity on circulating immune complex concentrations were studied in 14 transfusion experiments involving 12 patients with immune complex related diseases. Before erythrocyte transfusion circulating immune complex concentrations ranged from 8 to 128 micrograms/ml. After transfusion (2-3 units) immune complex concentrations decreased depending on the levels of CH50 titres in the recipients. In 11 experiments, in which the patients' CH50 titres ranged from 21 to 44, immune complex concentrations decreased by 75-100% within five days. The CH50 titres were also decreased after erythrocyte transfusion but subsequently increased to initial ranges within 6-35 days. In three patients with low CH50 titres (1.0-10.0) decreases in immune complexes were not observed. Direct Coombs' tests for IgG and C3 were performed before and after erythrocyte transfusion to determine potential in vivo binding of circulating immune complexes. Thus in eight of 14 experiments, in which erythrocytes carried no IgG before packed erythrocyte transfusion, seven became Coombs' positive for IgG after the transfusion. In seven of 14 experiments, in which erythrocytes were negative for complement before transfusion, five became positive afterwards. Moreover, in 12 instances slight increases of CR1 activity of patients' erythrocytes were observed within eight days, which improved further within 35 days after erythrocyte transfusion. These studies suggest that transfusion of erythrocytes with high CR1 activity results in the removal of circulating immune complexes and that this process is dependent on complement consumption. These experiments support the hypothesis that erythrocyte-CR1 has a functional role in the removal of circulating immune complexes and may thereby inhibit the deposition of immune complexes within body tissue constituents.

Antigen-Antibody Complex↗

Cinnarizine and flunarizine improve the tumour radiosensitisation induced by erythrocyte transfusion in anaemic mice.

The ability of the calcium antagonists, cinnarizine and flunarizine, to enhance the radiosensitisation produced by the administration of an erythrocyte transfusion to anaemic, RIF-1 or SCCVII/St tumour bearing mice was determined. Erythrocyte transfusion alone increased radiation cell killing 10-fold in the RIF-1 tumour when given 0-4 h before X-rays. In contrast, the SCCVII/St showed only a 4-fold increase in sensitivity, apparent when erythrocytes were given 2-6 h before irradiation. The administration of 50 mg kg-1 cinnarizine or flunarizine to anaemic mice followed by erythrocyte transfusion 0 h before X-rays produced the same level of cell survival for both tumours, a 20-fold increase in cell killing for cinnarizine, and a 30-40-fold effect for flunarizine, even though at this time interval, the erythrocyte transfusion alone did not sensitise the SCCVII/St tumour to X-rays. Further investigations indicated, however, that the erythrocyte transfusion was necessary to achieve the sensitisation with the calcium antagonists, since giving flunarizine to anaemic mice alone only achieved a 4-fold increase in radiation cell killing. In addition, flunarizine given with erythrocyte transfusion 4 h before X-rays, in SCCVII/St, the optimal time for radiosensitisation in this tumour, did not further increase the level of cell killing achieved by flunarizine plus erythrocyte transfusion 0 h before X-rays.

Anemia↗