Hunninghake G W, Fauci A S
Clin Exp Immunol. 1977 Mar;27(3):555-9.
The effect of cyclophosphamide on the absolute numbers and function of alveolar macrophages following either in vitro or in vivo drug exposure was studied in the guinea-pig. Two separate regimens of in vivo cyclophosphamide administration (100 mg/kg/one dose or 20 mg/kg for 5 days) both of which produce identical decreases in each population of peripheral blood leucocytes 5 days after the initial injection did not produce anay change in alveolar macrophage numbers when compared to control values. Neither a brief exposure to CY in vitro nor a brief exposure in vivo (100 mg/kg/one dose) caused any change in cytotoxic effector function of alveolar macrophages using the PHA-induced and antibody-dependent cellular cytotoxicity assays against sheep erythrocyte targets. In contrast, the more prolonged in vivo exposure to CY (20 mg/kg for 5 days), produced a significant decrease in the killer cell function of these cells. Thus, this study demonstrates that different regimens of cyclophosphamide administration, although producing similar degrees of peripheral blood leucopenia can produce markedly different effects on the functional capabilities of alveolar macrophages without quantitatively decreasing the absolute numbers of these cells.
在豚鼠中研究了环磷酰胺在体外或体内药物暴露后对肺泡巨噬细胞绝对数量和功能的影响。两种不同的体内环磷酰胺给药方案(100mg/kg/单次剂量或20mg/kg,连续5天),在初次注射后5天,两种方案都会使外周血白细胞各群体数量出现相同程度的下降,但与对照值相比,肺泡巨噬细胞数量未发生任何变化。无论是体外短暂暴露于环磷酰胺,还是体内短暂暴露(100mg/kg/单次剂量),使用针对绵羊红细胞靶标的PHA诱导的抗体依赖性细胞毒性试验,肺泡巨噬细胞的细胞毒性效应功能均未发生任何变化。相比之下,体内更长时间暴露于环磷酰胺(20mg/kg,连续5天),会使这些细胞的杀伤细胞功能显著降低。因此,本研究表明,不同的环磷酰胺给药方案,尽管会产生相似程度的外周血白细胞减少,但对肺泡巨噬细胞的功能能力可产生明显不同的影响,而不会使这些细胞的绝对数量出现定量减少。