Smith O M, Traul D L, Sieber F
Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226.
Exp Hematol. 1992 Dec;20(11):1278-84.
Merocyanine 540 (MC540) is a photosensitizing dye that has been used in several preclinical models and in a phase I clinical trial for the extracorporeal purging of tumor cells from autologous bone marrow grafts. The mechanism of the cytotoxic activity of MC540 is not yet fully understood, and the subcellular targets of MC540-mediated photodynamic damage remain to be identified. The human neutrophil provides an attractive model with which to study the effects of photoactivated MC540 on several well-defined cellular functions. As we report in this paper, simultaneous exposure of neutrophils to MC540 and light inhibited phagocytosis, random migration, chemotaxis, hydrogen peroxide production, and oxygen consumption. By contrast, the ability of neutrophils to kill engulfed bacteria and to produce superoxide radical was not compromised. Intracellular ATP levels and the activities of the cytosolic enzymes superoxide dismutase, catalase, and myeloperoxidase were only slightly reduced. Even in HL-60 leukemia cells, which bind more dye and are more readily killed by MC540-mediated photodynamic therapy than neutrophils, superoxide dismutase, catalase, and myeloperoxidase activities remained at normal or near-normal levels. These results are compatible with the view that plasma membrane components are primary targets of MC540-mediated photodynamic damage.
部花青540（MC540）是一种光敏染料，已用于多种临床前模型以及一项I期临床试验，用于从自体骨髓移植中体外清除肿瘤细胞。MC540细胞毒性活性的机制尚未完全了解，MC540介导的光动力损伤的亚细胞靶点仍有待确定。人类中性粒细胞为研究光激活的MC540对几种明确的细胞功能的影响提供了一个有吸引力的模型。正如我们在本文中所报道的，中性粒细胞同时暴露于MC540和光会抑制吞噬作用、随机迁移、趋化性、过氧化氢生成和氧气消耗。相比之下，中性粒细胞杀死被吞噬细菌和产生超氧自由基的能力并未受到损害。细胞内ATP水平以及胞质酶超氧化物歧化酶、过氧化氢酶和髓过氧化物酶的活性仅略有降低。即使在HL-60白血病细胞中，其比中性粒细胞结合更多的染料且更容易被MC540介导的光动力疗法杀死，超氧化物歧化酶、过氧化氢酶和髓过氧化物酶的活性仍保持在正常或接近正常水平。这些结果与质膜成分是MC540介导的光动力损伤的主要靶点这一观点相符。
