Photodynamic sterilization of red cells and its effect on contaminating white cells: viability and mechanism of cell death.
BACKGROUND
Phthalocyanines are useful sensitizers for photodynamic sterilization of red cell concentrates. Various lipid-enveloped viruses can be inactivated with only limited red cell damage. Because white cells are involved in the immunomodulatory effects of blood transfusions, the study of the effect of photodynamic treatment on these cells is imperative.


METHODS
White cell-enriched red cell suspensions were photodynamically treated with either the hydrophobic Pc4 (HOSiPcOSi-(CH3)2(CH2)3N(CH3)2) or water-soluble aluminum phthalocyanine tetrasulfonate (AIPCS4) under virucidal conditions. Viability of white cell subpopulations on Days 0, 1, and 4 after treatment was determined by fluorescence-activated cell sorting by flow cytometric analysis of propidium iodide uptake. Apoptosis induction was studied by DNA ladder formation and staining for an early marker of apoptosis (annexin V).


RESULTS
Treatment with Pc4 causes a significant decrease in cell viability of all white cells, as shown by prodidium iodide uptake. Monocytes and granulocytes are the most sensitive, and lymphocytes are relatively more resistant. Some of the cells die by apoptosis, which is induced within 30 minutes after treatment. Treatment with AIPCS4 damages only monocytes; other cell populations are not affected.


CONCLUSIONS
Physicochemical properties of the photosensitizers partly determine their effect on white cells. Differences in intracellular localization are likely to be responsible for the effects observed.
Moor
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AC
Department of Immunohematology, Leiden University Medical Center, The Netherlands. Dubbelman@mail.medfac.leidenuniv.nl
van der Veen
A
A
Dubbelman
T M
TM
VanSteveninck
J
J
Brand
A
A
D017304:Annexin A5 / Q000097:blood; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000097:blood; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D004905:Erythrocyte Aging / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D013242:Sterilization; D014775:Virus Activation / Q000187:drug effects
D017304:Annexin A5; D015415:Biomarkers; D004396:Coloring Agents; D007211:Indoles; D054833:Isoindoles; D011838:Radiation-Sensitizing Agents; C013647:phthalocyanine