Photofrin increases murine spleen cell transferrin receptor expression and responsiveness to recombinant myeloid and erythroid growth factors.
When given to normal male mice, the photochemotherapeutic agent Photofrin (porfimer sodium), a complex mixture of monomeric and oligomeric non-metallic porphyrins, significantly increased relative spleen weight, spleen cell numbers, DNA replication, levels of granulocyte-macrophage and erythroid progenitors and cellular responsiveness to different recombinant (r) myeloid growth factors. In contrast, monomeric hematoporphyrin had no effect on spleen weight, cellularity, erythroid progenitor levels or spleen cell cycle status. Photofrin significantly increased spleen cell expression of the receptor (CD71) for the iron transport protein transferrin by 72 h post-injection but did not affect levels of a receptor (CD25) for the T-cell growth factor interleukin-2 (IL-2) or spleen cell responsiveness to rIL-2. Further evidence of increased splenic erythropoietic activity in Photofrin-treated mice was provided by double color flow cytometric studies which indicated that the treatment elevated the number of nucleated spleen cells recognized by the erythroid lineage-specific monoclonal antibody TER-119. A majority of TER-119+ cells also expressed CD71 and the heat stable antigen, a marker of developing hematopoietic cells as well as mature erythrocytes. The capacity of Photofrin to stimulate murine hematopoietic activity appears to be a property not shared by other porphyrin photosensitizers.
Hunt
D W
DW
QLT PhotoTherapeutics, Inc., Vancouver, BC, Canada. dhunt@qlt-pdt.com
Jiang
H
H
Levy
J G
JG
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D017323:Dihematoporphyrin Ether / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015672:Erythroid Precursor Cells / Q000187:drug effects; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D006415:Hematoporphyrins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009929:Organ Size / Q000187:drug effects; D017319:Photosensitizing Agents / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000235:genetics; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D003115:Colony-Stimulating Factors; D006415:Hematoporphyrins; D017319:Photosensitizing Agents; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017323:Dihematoporphyrin Ether