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经血卟啉衍生物光动力学激活的巨噬细胞的杀瘤能力

Tumoricidal capacities of macrophages photodynamically activated with hematoporphyrin derivative.

作者信息

Yamamoto N, Hoober J K, Yamamoto N, Yamamoto S

机构信息

Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140.

出版信息

Photochem Photobiol. 1992 Aug;56(2):245-50. doi: 10.1111/j.1751-1097.1992.tb02153.x.

DOI:10.1111/j.1751-1097.1992.tb02153.x
PMID:1386933
Abstract

Four days after administration to mice of small amounts (30-600 ng/mouse) of hematoporphyrin derivative (HPD), peritoneal macrophages exhibited a greatly enhanced Fc-receptor mediated phagocytic capacity as assayed by ingestion activity of IgG-coated sheep erythrocytes. Much higher doses (greater than 3000 ng/mouse) did not have this effect. The peritoneal macrophages activated by administration of HPD have tumoricidal capacity for IgG-coated retinoblastoma cells. We then studied in vitro photodynamic activation of macrophages by white and red fluorescent light irradiation of mouse peritoneal cells (mixture of macrophages and B and T lymphocytes) in media containing very low concentrations of HPD. A short (5 s) white fluorescent light exposure (1Wm-2) of peritoneal cells in a medium containing 0.03 ng HPD/mL produced the maximal level of ingestion activity of macrophages. A 15 s red fluorescent light exposure (1Wm-2) of peritoneal cells in a medium containing 0.1 ng HPD/mL produced the maximal level of ingestion activity of macrophages. Thus, photodynamic activation of macrophages with white fluorescent light is more efficient than that with red fluorescent light. This can be explained by the fact that HPD has a large absorption peak at about 364 nm which extends into the visible range, and decreasingly smaller absorption bands at 500, 535, 570 and 630 nm. In vitro photodynamically activated macrophages showed efficient tumoricidal activity regardless of the type (white or red) of light used. These results suggest that a low level of HPD promotes therapeutic immunopotentiation.

摘要

给小鼠注射少量(30 - 600纳克/只)血卟啉衍生物(HPD)四天后,通过IgG包被的绵羊红细胞摄取活性测定,腹膜巨噬细胞表现出Fc受体介导的吞噬能力大大增强。更高剂量(大于3000纳克/只)则没有这种效果。通过给予HPD激活的腹膜巨噬细胞对IgG包被的视网膜母细胞瘤细胞具有杀瘤能力。然后,我们在含有极低浓度HPD的培养基中,通过对小鼠腹膜细胞(巨噬细胞与B淋巴细胞和T淋巴细胞的混合物)进行白色和红色荧光照射,研究巨噬细胞的体外光动力激活。在含有0.03纳克HPD/毫升的培养基中,对腹膜细胞进行短时间(5秒)白色荧光照射(1瓦/平方米)可使巨噬细胞的摄取活性达到最高水平。在含有0.1纳克HPD/毫升的培养基中,对腹膜细胞进行15秒红色荧光照射(1瓦/平方米)可使巨噬细胞的摄取活性达到最高水平。因此,用白色荧光对巨噬细胞进行光动力激活比用红色荧光更有效。这可以用以下事实来解释:HPD在约364纳米处有一个大的吸收峰,该峰延伸到可见光范围,在500、535、570和630纳米处有逐渐变小的吸收带。无论使用何种类型(白色或红色)的光,体外光动力激活的巨噬细胞都显示出有效的杀瘤活性。这些结果表明,低水平的HPD可促进治疗性免疫增强。

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