Inhibition by albumin of merocyanine 540-mediated photosensitization of platelets and viruses.
The effect of the photosensitizer merocyanine 540 (MC 540) on platelets and on three marker viruses was examined to assess its potential in reducing virus transmission by blood products. The results demonstrated several deleterious effects of MC 540 (4-24 micrograms/mL) on platelet morphology and function in both the absence and presence of light (450-600 nm). Treatment of washed platelets with MC 540 in the dark resulted in a significant release of serotonin in the absence of added agonist, as well as a diminished response to thrombin as measured in vitro. In addition, photosensitization caused spontaneous platelet aggregation and release of 92 percent of the releasable serotonin without the addition of an agonist. Because photo-treatment of blood products is likely to be performed in a protein-rich medium, the influence of albumin on the phototoxic effects on platelets was assessed. Albumin added to the suspension medium at concentrations greater than or equal to 1.0 percent protected the platelets against the effects of MC 540 in the dark, whereas 5-percent albumin was required for protection against the phototoxic effects of MC 540 on the platelet response to thrombin. The antiviral activity of MC 540 and light was examined by using the lipid-containing viruses herpes simplex virus (HSV) and bacteriophages phi 6 and PM2. Of the lipid-enveloped viruses, HSV was 25 times more photosensitive to MC 540 than was phi 6 (15 micrograms/mL). PM2, which has an internal lipid layer, was almost 300 times less sensitive to MC 540 and light than was HSV.(ABSTRACT TRUNCATED AT 250 WORDS)
Prodouz
K N
KN
Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland.
Lytle
C D
CD
Keville
E A
EA
Budacz
A P
AP
Vargo
S
S
Fratantoni
J C
JC
D001435:Bacteriophages / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008027:Light; D010974:Platelet Aggregation / Q000187:drug effects* / Q000528:radiation effects; D011549:Pseudomonas / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D011744:Pyrimidinones / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012701:Serotonin / Q000097:blood; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
D011744:Pyrimidinones; D011838:Radiation-Sensitizing Agents; D012710:Serum Albumin, Bovine; D012701:Serotonin; C003954:merocyanine dye; D007770:L-Lactate Dehydrogenase