The lipophilic photosensitizer, merocyanine 540 (MC) has been proposed for use as an agent to reduce the transmission of virus by cellular blood components. In a previous study, we demonstrated the antiviral activity of MC in the presence of visible light (450-600nm). The inactivation of lipid-enveloped viruses by dye and light is most likely mediated by reactive singlet oxygen. Platelets are highly susceptible to photodamage by MC and demonstrate marked morphological alterations, a disruption of the normal response to agonists, and a spontaneous release of granule contents. Significant photodamage to the platelet membrane upon treatment with dye and light has been demonstrated in studies of MC binding to membranes in the absence of presence of exogenous albumin, by measurements of arachidonic acid release from membranes, and by SDS-polyacrylamide gel electrophoretic (SDS-PAGE) analyses of alterations of the migration of membrane proteins following treatment. In addition, MC + light caused the generation of microvesicles (MV) from membranes, indicating activation of platelets. Patterns of MV protein composition were analyzed by SDS-PAGE and were found to be significantly different in MV generated with MC + light vs. minus light. Individual proteins incorporated into MV were identified by immunoblotting using antibodies to major platelet glycoproteins, cytoskeletal proteins and granule proteins. In addition, MC + light caused the formation of a high molecular weight membrane protein complex which has been analyzed by size exclusion chromatography and 2- dimensional isoelectric focusing and SDS-PAGE. Results of this study were presented at the annual meeting of the American Society for Photobiology in June, 1991 and were published in Blood Cells, in December, 1991.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Intramural Research (Z01)
Project #
1Z01BH001009-04
Application #
3792609
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Center Biologics Evaluation Research Hematology
Department
Type
DUNS #
City
State
Country
United States
Zip Code