Abstract

The photosensitizer benzoporphyrin-derivative monoacid ring A (BPD-MA, verteporfin), in combination with visible light irradiation, a clinical procedure termed photodynamic therapy (PDT), has immunomodulatory activity in various mouse models. We studied the impact of BPD-MA and light upon DBA/2 mouse splenic dendritic cells (DC), a potent antigen-presenting cell (APC) type. DC treated with nanomolar amounts of BPD-MA and 690 nm wavelength light had a reduced capacity to stimulate the proliferation of alloreactive T cells. Treatment with BPD-MA and light reduced DC levels of major histocompatibility (MHC) Class I and II antigens, intercellular adhesion molecule-1 (ICAM-1, CD54), the costimulatory B7-1 (CD80) and B7-2 (CD86) molecules, leucocyte common antigen CD45, the apoptosis-regulating Fas (CD95) receptor and the integrin CD11c. In contrast, DC expression of leucocyte function-associated-1 (LFA-1, CD11a), Mac-1 (CD11b), integrin beta2 chain (CD18) and the DEC-205 receptor increased, while CD40 levels were relatively unchanged 24 h after the treatment. MHC Class I and ICAM-1 levels decreased to 40% of control levels within 2 h following the photodynamic treatment. In the absence of light, BPD-MA did not affect DC receptor levels. Changes in DC receptor levels produced by BPD-MA and red light were similar to those produced by ultraviolet B light irradiation. The photodynamic treatment of activated splenic B cells, a separate APC class, had little effect upon receptor expression, except that MHC Class II levels were moderately decreased 24 h later. Changes in DC receptor expression may contribute to the immunomodulatory action of PDT.

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