title: Inhibitory effects of merocyanine 540-mediated photodynamic therapy on cellular immune functions: A role in the prophylaxis of graft-versus-host disease?
abstract: Merocyanine 540-mediated photodynamic therapy (MC540-PDT) has been used in clinical trials for the purging of autologous hematopoietic stem cell grafts. When the same combinations of dye and light were applied to human peripheral blood lymphocytes, a broad range of T- and B-cell functions were impaired, prompting speculations about a potential role of MC540-PDT in the prophylaxis of graft-versus-host disease (GVHD). We here report on the effects of MC540-PDT on in vitro functions of murine lymphocytes as well as a preliminary evaluation of MC540-PDT for the prevention of GVHD in murine models of allogeneic bone marrow transplantation. Mixed lymphocyte reactions, proliferative responses to lectins, interleukin-2 and lipopolysaccharide, T-cell-mediated lysis, and NK activity were all inhibited by moderate doses of MC540-PDT. Whether MC540-PDT reduced the incidence and/or the severity of GVHD in murine models of allogeneic hematopoietic stem cell transplantation depended on the composition of the mismatched grafts and the intensity of the preparative regimen. MC540-PDT was only beneficial (i.e. reduced the incidence and/or severity of GVHD) when the spleen cell content of grafts was low and/or the radiation dose of the preparative regimen was not myeloablative, and, therefore, may have encouraged mixed chimerism.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: dltraul@msn.com.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Traul
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: fsieber@mcw.edu.
authors.forename: Fritz
authors.initials: F
authors.lastname: Sieber
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011744:Pyrimidinones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D014184:Transplantation, Homologous
chemical_list: D017319:Photosensitizing Agents; D011744:Pyrimidinones; C003954:merocyanine dye
keywords: Graft-versus-host disease; Hematopoietic stem cell transplantation; Merocyanine 540; Mixed chimerism; Photodynamic therapy