Population dynamics of natural killer cells and T lymphocytes in murine spleen and bone marrow during the development of erythroleukemia: the effect of indomethacin.
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.
Miller
S C
SC
Department of Anatomy, McGill University, Montreal, Canada.
Christopher
F L
FL
Dussault
I
I
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D007213:Indomethacin / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009928:Organ Specificity; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
D007213:Indomethacin