Photodynamic Effects with 5-Aminolevulinic Acid on Cytokines and Exosomes in Human Peripheral Blood Mononuclear Cells

Abstract

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a precursor to the potent photosensitizer, protoporphyrin IX (PpIX), is an established modality for several malignant and premalignant diseases. This treatment is based on the light-activated PpIX in targeted lesions. Although numerous studies have confirmed the necrosis and apoptosis involved in the mechanism of action of this modality, little information is available for the change of exosome levels after treatment. We report from the first study on the effects of ALA-PDT on cytokines and exosomes of human healthy peripheral blood mononuclear cells (PBMCs). The treatment reduced the cytokines and exosomes studied, although there was variation among individual PBMC samples. This reduction is consistent with PDT-mediated survivals of subsets of PBMCs. More specifically, the ALA-PDT treatment apparently decreased all pro-inflammatory cytokines included, suggesting that this treatment may provide a strong anti-inflammatory effect. In addition, the treatment has decreased the levels of different types of exosomes, the HLA-DRDPDQ exosome in particular, which plays an important role in the rejection of organ transplantation as well as autoimmune diseases. These results may suggest future therapeutic strategies of ALA-PDT.

Photodynamic Effects with 5-Aminolevulinic Acid on Cytokines and Exosomes in Human Peripheral Blood Mononuclear Cells from Patients with Crohn’s Disease

“…CD326 and SSEA-4 exosomes are biomarkers for organ transplantation rejection [64,65]. Downregulation of these two exosomes following ALA-PDT may suggest a beneficial effect and is in agreement with the results of our previous report [57]. CD105 or endoglin (ENG) found in endothelial cells is associated with angiogenesis [66] whereas CD142, CD41b, and CD42a participate in blood coagulation cascades.…”

“…Technically, however, isolation of exosomes can be challenging. In this study we used a bead-based technique [56], the same as described in our published report [57].…”

Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study

“…Consequently, upon light irradiation, these abnormally proliferative cells are selectively destroyed while resting normal T-cells remain unaffected so that ALA-ECP may result in more effective elimination of diseased T-cells compared to conventional ECP with 8-MOP/UVA. (2) Induction of anti-tumor immunity [ 24 , 25 ]. ECP with ALA has the potential to stimulate anti-tumor immune responses, contributing to the overall therapeutic efficacy.…”

Virtual-freezing fluorescence imaging flow cytometry with 5-aminolevulinic acid stimulation and antibody labeling for detecting all forms of circulating tumor cells

“…Fourth, ~100% of HT-29 cells and ~96% of HT-1080 cells were regarded as PpIX-positive cells, which can be interpreted as almost all cancer cells being active. Lastly, ~15% of the PBMCs were PpIX-positive cells, which can be explained by the presence of monocytes with CD14 expression that are known to accumulate PpIX when treated with 5-ALA 35 . These results show that our VIFFI flow cytometer has the ability to detect fluorescence signals from EpCAM-FITC, CD45-PE, and PpIX correctly.…”