Horowitz B, Rywkin S, Margolis-Nunno H, Williams B, Geacintov N, Prince A M, Pascual D, Ragno G, Valeri C R, Huima-Byron T
New York Blood Center, New York 10021.
Blood Cells. 1992;18(1):141-9; discussion 150.
Aluminum phthalocyanine tetrasulfonates (AIPcS) are photoactive compounds with absorption maxima at 665-675 nm. The inactivation of viruses (vesicular stomatitis virus, VSV; human immunodeficiency virus, HIV) added to either whole blood or red blood cell concentrates (RBCC) and platelet concentrates (PC) on treatment with tetrasulfonated AIPc (AIPcS4) was evaluated. Treatment of RBCC with 10 microM AIPcS4 and 44 J/cm2 visible light resulted in the inactivation of greater than or equal to 10(5.5) infectious doses (TCID50) of cell-free VSV, greater than or equal to 10(5.6) TCID50 of cell-associated VSV, and greater than or equal to 10(4.7) TCID50 of cell-free sindbis virus. Both greater than or equal to 10(4.2) TCID50 of cell-free and greater than or equal to 10(3.6) TCID50 of cell-associated forms of HIV were also shown to be inactivated. Encephalomyocarditis virus, used as a model for nonenveloped viruses, was not inactivated. Equivalent virus kill with Photofrin II required a substantially higher concentration of dye and longer exposure to visible light. Following AIPcS4 treatment, red cell integrity was well maintained as judged by the low level (less than 2%) of hemoglobin release immediately following treatment and on subsequent storage, by measurements of erythrocyte osmotic fragility, and by the normal recovery and circulatory survival on infusion of treated, autologous red blood cells in baboons. Treatment of PC with 10 microM AIPcS4 and 44 J/cm2 visible light also resulted in effective virus kill (greater than or equal to 10(5.5) TCID50) of VSV; however, both the rate and extent of platelet aggregation in response to collagen addition declined by at least 50%. Based on these results, further characterization of AIPcS4-treated RBCC is justified.
四磺化铝酞菁(AIPcS)是一类光活性化合物,其吸收峰在665 - 675纳米处。对添加到全血、红细胞浓缩液(RBCC)和血小板浓缩液(PC)中的病毒(水疱性口炎病毒,VSV;人类免疫缺陷病毒,HIV),在用四磺化AIPc(AIPcS4)处理后的灭活情况进行了评估。用10微摩尔/升的AIPcS4和44焦/平方厘米的可见光处理RBCC,可使游离型VSV的灭活程度达到大于或等于10(5.5)感染剂量(半数组织培养感染剂量,TCID50),细胞相关型VSV大于或等于10(5.6) TCID50,游离型辛德毕斯病毒大于或等于10(4.7) TCID50。游离型HIV大于或等于10(4.2) TCID50以及细胞相关型HIV大于或等于10(3.6) TCID50也都显示被灭活。用作非包膜病毒模型的脑心肌炎病毒未被灭活。使用卟吩姆钠实现同等的病毒杀灭效果需要更高浓度的染料以及更长时间的可见光照射。在AIPcS4处理后,通过处理后及后续储存时血红蛋白低水平释放(低于2%)、红细胞渗透脆性测量以及将处理后的自体红细胞输注到狒狒体内后的正常恢复和循环存活情况判断,红细胞完整性得到了良好维持。用10微摩尔/升的AIPcS4和44焦/平方厘米的可见光处理PC,也能有效杀灭VSV(大于或等于10(5.5) TCID50);然而,添加胶原蛋白后血小板聚集的速率和程度至少下降了50%。基于这些结果,对经AIPcS4处理的RBCC进行进一步表征是合理的。