Miller S C, Christopher F L, Dussault I
Department of Anatomy, McGill University, Montreal, Canada.
Nat Immun. 1992 Mar-Apr;11(2):78-91.
Quantitative and functional methods were used to assess changes in NK (ASGM-1+, nonblast, lymphoid) cells and cytotoxic/suppressor T (Lyt-2+) cells in the spleen and bone marrow (BM) of normal DBA/2 mice and/or mice bearing early (7 days)- and late (14 days)-stage erythroleukemia +/- concomitant oral administration of indomethacin. In normal mice, indomethacin increased ASGM-1+ cells in the spleen and BM by 7 days of continuous drug administration relative to control, while the numbers of Lyt-2+ cells in both organs remained unaltered. The presence of a tumor in untreated mice resulted, by 14 days development, in elevated numbers of ASGM-1+ cells in the spleen and BM. Lyt-2+ cells in the spleen increased transiently (7 days) in tumor-bearing (TB) mice and returned to normal levels by 14 days TB. No difference in either early- or late-stage TB was observed in the numbers of Lyt-2+ cells in the BM. In spleen and BM of TB mice, indomethacin increased ASGM-1+ cells by 7 days TB. ASGM-1+ cells returned to untreated levels by 14 days TB in both organs in spite of continued drug treatment. The numbers of Lyt-2+ cells in both the spleen and BM of 7 days indomethacin-treated TB mice were reduced relative to those of untreated TB mice. By 14 days TB, drug treatment had no effect on Lyt-2+ cell numbers in the spleen or BM. Spontaneous cytolytic activity of the spleen and BM did not always parallel changes in the numbers of ASGM-1+ cells, indicating the presence of late, immature, prelytic NK cells among the ASGM-1+ cell numbers. The results demonstrate that the numbers of NK and cytotoxic/suppressor T cells are markedly but differentially affected during tumor growth and/or time of exposure to indomethacin in an organ-specific manner.
采用定量和功能方法评估正常DBA/2小鼠和/或患有早期(7天)和晚期(14天)红白血病且伴有或不伴有吲哚美辛口服给药的小鼠脾脏和骨髓中NK(ASGM-1+、非原始、淋巴细胞样)细胞以及细胞毒性/抑制性T(Lyt-2+)细胞的变化。在正常小鼠中,连续给药7天时,相对于对照组,吲哚美辛使脾脏和骨髓中的ASGM-1+细胞增加,而两个器官中Lyt-2+细胞的数量保持不变。未治疗小鼠在肿瘤发生14天时,脾脏和骨髓中ASGM-1+细胞数量增加。荷瘤(TB)小鼠脾脏中的Lyt-2+细胞短暂增加(7天),并在荷瘤14天时恢复到正常水平。骨髓中Lyt-2+细胞数量在早期或晚期荷瘤小鼠中均未观察到差异。在荷瘤小鼠的脾脏和骨髓中,吲哚美辛在荷瘤7天时增加了ASGM-1+细胞。尽管持续药物治疗,但在14天时两个器官中的ASGM-1+细胞均恢复到未治疗水平。吲哚美辛治疗7天的荷瘤小鼠脾脏和骨髓中Lyt-2+细胞数量相对于未治疗的荷瘤小鼠减少。到荷瘤14天时,药物治疗对脾脏或骨髓中Lyt-2+细胞数量没有影响。脾脏和骨髓的自发细胞溶解活性并不总是与ASGM-1+细胞数量的变化平行,表明在ASGM-1+细胞数量中存在晚期、未成熟、裂解前的NK细胞。结果表明,在肿瘤生长和/或接触吲哚美辛期间,NK细胞和细胞毒性/抑制性T细胞数量受到显著但不同的影响,且具有器官特异性。