Photofrin® increases murine spleen cell transferrin receptor expression and responsiveness to recombinant myeloid and erythroid growth factors

• Published in: Immunopharmacology Vol. 38; no. 3; pp. 267 - 278
• Main Authors: Hunt, David W.C, Jiang, Huijun, Levy, Julia G
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.01.1998; Elsevier
• Subjects: Animals; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Cycle - drug effects; Cell Division - drug effects; Cell physiology; Colony-Stimulating Factors - pharmacology; Dihematoporphyrin Ether - pharmacology; Epidermal Growth Factor - pharmacology; Erythroid Precursor Cells - drug effects; Erythropoiesis; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Granulocyte-Macrophage Colony-Stimulating Factor - analysis; Hematopoiesis; Hematoporphyrins - pharmacology; Male; Medical sciences; Mice; Mice, Inbred DBA; Molecular and cellular biology; Organ Size - drug effects; Photofrin; Photoradiation therapy and photosensitizing agent; Photosensitizing Agents - pharmacology; Receptors, Interleukin-2 - drug effects; Receptors, Interleukin-2 - genetics; Receptors, Transferrin - biosynthesis; Receptors, Transferrin - drug effects; Recombinant Proteins - pharmacology; Responses to growth factors, tumor promotors, other factors; Spleen; Spleen - cytology; Spleen - drug effects; Spleen - metabolism; Transferrin receptor; Treatment with physical agents; Treatment. General aspects; Tumors; Erythropoiesis; PWM-SCCM, pokeweed mitogen spleen cell-conditioned medium; CFU-GM, colony forming unit, granulocyte-macrophage; HSA, heat stable antigen; TrfR, transferrin receptor; M-CSF, macrophage colony stimulating factor; HVD, hydroxyvinylethyl deuteroporphyrin; PBS, phosphate-buffered saline; CD, cluster of differentiation; Hematopoiesis; IMDM, Iscove's modified Dulbecco's medium; BFU-E, burst forming unit, erythroid; Spleen; BSA, bovine serum albumin; GM-CSF, granulocyte-macrophage colony stimulating factor; G-CSF, granulocyte colony stimulating factor; PI, propidium iodide; FITC, fluorescein isothiocyanate; MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; Photofrin; Hp, hematoporphyrin; r, recombinant; Transferrin receptor; 2-ME, 2-mercaptoethanol; PE, phycoerythrin; CFU-E, colony forming unit, erythroid; i.p., intraperitoneal; IL, interleukin; IL-2R, interleukin-2 receptor; Epo, erythropoietin; FACS, fluorescence-activated cell sorter analysis; FCS, fetal calf serum; Transferrin; Intraperitoneal administration; Rodentia; Cytokine; Gene expression; Hematoporphyrin; Colony forming cell; Phototherapy; Porfimer sodium; Vertebrata; Mammalia; Treatment; Interleukin 2; Mouse; Porphyrin; Animal; Recombinant protein; Photosensitizer; Growth factor; Biological receptor
• ISSN: 0162-3109
• DOI: 10.1016/S0162-3109(97)00086-6

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.