McCloud C M, Beard T L, Kacew S, Reasor M J
Department of Pharmacology and Toxicology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, USA.
Exp Mol Pathol. 1995 Feb;62(1):12-21. doi: 10.1006/exmp.1995.1002.
Chlorphentermine (CP) is a cationic, amphiphilic drug (CAD) that has been studied widely for its ability to induce phospholipidosis, a disorder characterized by excessive accumulation of cellular phospholipid and ultrastructural development of lysosomal lamellar bodies (LLBs) in the cell. The accumulation of inducing drug correlates with increasing phospholipids. In the present study, we examined the reversibility of this disorder in rat alveolar macrophages (AMs) following a 7-day treatment (30 mg/kg/day, ip). The reversibility of phospholipidosis was examined under in vivo conditions and under in vitro conditions in cell cultures for a period of up to 12 days. There was a marked reduction in cellular CP levels and phospholipid content after 4 days of recovery, both in vivo and in vitro; however, there was no indication of significant loss of LLBs. Beyond this time point, ultrastructural recovery from phospholipidosis lagged behind the biochemical recovery temporally and was somewhat less rapid in vitro than in vivo. By 12 days of recovery, AMs from both groups had recovered biochemically, but a moderate level of LLBs was still present in some AMs in the in vitro recovery group. The results of this study indicate that there are more similarities than differences when comparing the recovery of phospholipidotic cells in vitro to that occurring in vivo. We conclude that the use of cell cultures may prove valuable in studying the reversibility of CAD-induced phospholipidosis.
氯苯丁胺（CP）是一种阳离子两亲性药物（CAD），因其诱导磷脂沉积症的能力而受到广泛研究。磷脂沉积症是一种以细胞内磷脂过度积累和溶酶体板层小体（LLBs）超微结构发育为特征的疾病。诱导药物的积累与磷脂增加相关。在本研究中，我们检查了大鼠肺泡巨噬细胞（AMs）在7天治疗（30mg/kg/天，腹腔注射）后这种疾病的可逆性。在体内条件和细胞培养的体外条件下，对磷脂沉积症的可逆性进行了长达12天的检查。在体内和体外恢复4天后，细胞CP水平和磷脂含量均显著降低；然而，没有迹象表明LLBs有明显损失。超过这个时间点，从磷脂沉积症的超微结构恢复在时间上落后于生化恢复，并且在体外比在体内恢复得稍慢。到恢复12天时，两组的AMs在生化方面均已恢复，但在体外恢复组的一些AMs中仍存在中等水平的LLBs。本研究结果表明，比较体外磷脂沉积细胞的恢复与体内发生的情况时，相似之处多于差异。我们得出结论，细胞培养的应用可能在研究CAD诱导的磷脂沉积症的可逆性方面具有价值。
