Quinacrine Enhances Vesicular Stomatitis Virus Inactivation and Diminishes Hemolysis of Dimethylmethylene Blue–phototreated Red Cells ¶

Several photodynamic methods for virus inactivation in red blood cell (RBC) suspensions have resulted in unwanted hemolysis during extended 1–6°C storage. To explore the possibility that hemolysis may be mediated by a membrane‐bound dye, a molecule similar in structure to yet different in light absorption properties from the photosensitizer was used as an inhibitor for RBC membrane binding in virus photoinactivation and photohemolysis studies. The addition of 500 μM quinacrine to oxygenated RBC before treatment with 3.6 μM dimethylmethylene blue (DMMB) and 219 mJ/cm2 red light resulted in an increased extracellular concentration of the sensitizer, increased extracelluar viral inactivation kinetics, and decreased hemolysis during 1–6°C storage without alteration of quinacrine absorption properties. These results collectively suggest that despite its recognized affinity for viral nucleic acid, DMMB also binds to RBC membranes and that the bound dye is, in part, responsible for photoinduced hemolysis.

[1]  S. Stramer,et al.  Current prevalence and incidence of infectious disease markers and estimated window‐period risk in the American Red Cross blood donor population , 2002, Transfusion.

[2]  S. Wagner,et al.  Duck hepatitis B photoinactivation bydimethylmethylene blue in RBC suspensions , 2001, Transfusion.

[3]  T. Dubbelman,et al.  Selective protection of RBCs against photodynamic damage by the band 3 ligand dipyridamole , 2000, Transfusion.

[4]  C. Hays.  The United States Army and malaria control in World War II. , 2000, Parassitologia.

[5]  D. Meruelo,et al.  Strategies for Evaluation of Enveloped Virus Inactivation in Red Cell Concentrates Using Hypericin , 2000, Photochemistry and photobiology.

[6]  T. Mohammad,et al.  Photonuclease activity of Taylor's blue. , 1999, Bioorganic & medicinal chemistry letters.

[7]  P. Kinnunen,et al.  Binding of quinacrine to acidic phospholipids and pancreatic phospholipase A2. Effects on the catalytic activity of the enzyme. , 1998, Biochemistry.

[8]  L. Cincotta,et al.  Preservation of red cell properties after virucidal phototreatment with dimethylmethylene blue , 1998, Transfusion.

[9]  L. Cincotta,et al.  Factors Affecting Virus Photoinactivation by a Series of Phenothiazine Dyes , 1998, Photochemistry and photobiology.

[10]  C. Högman,et al.  Clinical and Laboratory Experience with Erythrocyte and Platelet Preparations from a 0.5CPD Erythro‐Sol Opti System , 1997, Vox sanguinis.

[11]  A. Moor,et al.  Shelf‐life of photodynamically sterilized red cell concentrates with various numbers of white cells , 1997, Transfusion.

[12]  S. Kleinman,et al.  The Risk of Transfusion-Transmitted Viral Infections , 1996 .

[13]  N. Geacintov,et al.  Virus inactivation in red cell concentrates by photosensitization with phthalocyanines: protection of red cells but not of vesicular stomatitis virus with a water‐soluble analogue of vitamin E , 1995, Transfusion.

[14]  C. Högman,et al.  Half‐Strength Citrate CPD Combined with a New Additive Solution for Improved Storage of Red Blood Cells Suitable for Clinical Use , 1993, Vox sanguinis.

[15]  B. Nordén,et al.  Ionic strength dependence of the binding of methylene blue to chromatin and calf thymus DNA. , 1992, Journal of biomolecular structure & dynamics.

[16]  N. Geacintov,et al.  Inactivation of viruses in red cell and platelet concentrates with aluminum phthalocyanine (AIPc) sulfonates. , 1992, Blood cells.

[17]  T. Okunaka,et al.  Correlation between photodynamic efficacy of differing porphyrins and membrane partitioning behavior , 1992, Lasers in surgery and medicine.

[18]  D. Gaffney,et al.  Evaluation of merocyanine 540-sensitized photoirradiation as a means to inactivate enveloped viruses in blood products. , 1990, The Journal of laboratory and clinical medicine.

[19]  J. Levy,et al.  Development of a model to demonstrate photosensitizer‐mediated viral inactivation in blood , 1990, Transfusion.

[20]  J. Kopferschmitt,et al.  Clinical Features and Management of Poisoning due to Antimalarial Drugs , 1987, Medical toxicology and adverse drug experience.

[21]  J. Burch,et al.  Direct interaction of mepacrine with erythrocyte and platelet membrane phospholipid. , 1982, The Journal of biological chemistry.

[22]  H. Murray,et al.  Quinacrine-induced psychiatric disturbances. , 1982, Southern medical journal.

[23]  N. Kallenbach,et al.  Frameshift mutagenesis of 9-aminoacridine derivatives in Salmonella typhimurium. , 1981, Mutation research.

[24]  P. Epstein,et al.  Local anesthetics, mepacrine, and propranolol are antagonists of calmodulin. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[25]  T. Greenwalt,et al.  Evaluation of Toluidine Blue for Measuring Erythrocyte Membrane Loss during in Vivo Ageing , 1978, British journal of haematology.

[26]  N. Schoene.  Properties of platelet phospholipase A2. , 1978, Advances in prostaglandin and thromboxane research.

[27]  D. Vanderjagt,et al.  Use of tetramethylbenzidine in plasma hemoglobin assay. , 1977, Clinical chemistry.

[28]  M. Sass,et al.  Metabolic changes in stored blood measured by methylene blue. , 1968, Clinica chimica acta; international journal of clinical chemistry.