Hunt D W, Sorrenti R A, Smits C B, Levy J G
Department of Microbiology, University of British Columbia, Vancouver, Canada.
Immunopharmacology. 1993 Nov-Dec;26(3):203-12. doi: 10.1016/0162-3109(93)90036-p.
This report describes the effects of the porphyrin photosensitizers, Photofrin and benzoporphyrin derivative (BPD) on the immunohematopoietic system of normal and immunosuppressed DBA/2 mice in the absence of activating light. Photofrin (10 and 25 mg/kg) significantly increased in vitro colony formation by cells of the granulocyte-macrophage lineage in the spleen and bone marrow. Splenic hypercellularity, splenomegaly and elevated levels of blood leukocytes were observed in these mice 7 days following Photofrin injection. Evidence that Photofrin influenced the lymphohematopoietic compartment was suggested by a significant increase in blood lymphocytes and a population of spleen cells identified by a monoclonal antibody (LR-1) reactive with mouse splenic B lymphocytes. Proliferative responses of spleen cells from Photofrin-treated mice to sub-optimal concentrations of Con A were greater than that observed for controls. However, spleen cell responses to LPS were unaltered by Photofrin administration. In contrast, BPD (10 mg/kg) did not alter any of the immunohematopoietic parameters studied. When Photofrin was administered to mice treated with the myeloablative agent 5-FU there was a significant acceleration in the recovery of total blood leukocyte and spleen cell numbers, relative to the controls. These studies demonstrate that, in addition to its previously documented activities as a photosensitizer, Photofrin can exert stimulatory effects upon murine hematopoiesis.
本报告描述了在无激活光的情况下,卟啉光敏剂光卟啉(Photofrin)和苯并卟啉衍生物(BPD)对正常及免疫抑制的DBA/2小鼠免疫造血系统的影响。光卟啉(10和25毫克/千克)显著增加了脾脏和骨髓中粒细胞-巨噬细胞系细胞的体外集落形成。在注射光卟啉7天后,这些小鼠出现脾细胞增多、脾肿大和血液白细胞水平升高。血液淋巴细胞显著增加以及一种可与小鼠脾脏B淋巴细胞反应的单克隆抗体(LR-1)识别的脾细胞群体增多,提示光卟啉影响了淋巴造血区室。光卟啉处理小鼠的脾细胞对亚最佳浓度刀豆蛋白A(Con A)的增殖反应大于对照组。然而,光卟啉给药并未改变脾细胞对脂多糖(LPS)的反应。相比之下,BPD(10毫克/千克)并未改变所研究的任何免疫造血参数。当给用骨髓消融剂5-氟尿嘧啶(5-FU)处理的小鼠施用光卟啉时,相对于对照组,全血白细胞和脾细胞数量的恢复显著加速。这些研究表明,除了其先前记录的作为光敏剂的活性外,光卟啉还可对小鼠造血产生刺激作用。