Moqattash S, Abraham N G, Lutton J D
Department of Human and Clinical Anatomy, College of Medicine, Sultan Qaboos University, Muscat, Oman.
Leuk Res. 1994 Jul;18(7):531-9. doi: 10.1016/0145-2126(94)90091-4.
A leukemoid reaction occurs after inoculation of L1210 leukemic cells into recipient mice and the degree of granulocytosis is correlated with tumor progression. It was found that the sera of leukemic mice contained elevated levels of colony stimulating activity (CSA) when compared with normal mouse sera. Media conditioned by L1210 cells in vitro (L1210-CM) contained CSA which stimulated normal bone marrow myeloid colony growth and an auto-stimulatory activity (ASA) which stimulated L1210 cell proliferation. We studied the effects of trans-retinoic acid (RA) and 1,25 dihydroxyvitamin D3 (VD3) on the production of growth substances by L1210 cells. When L1210-CM was prepared in the presence of RA and VD3, the CSA and ASA were markedly inhibited. A combination of the two agents was more effective than either agent. Mice inoculated with 1 x 10(5) L1210 suspension culture cells treated with either agent or both combined survived significantly longer than controls. Mice inoculated with L1210 cells treated with the two agents combined survived longest. By using antibodies, preliminary analysis of growth substances generated in L1210-CM showed that it contains primarily GM-CSF and M-CSF-like activities which were distinct from ASA. Combination antibody titer assays revealed that ASA was not significantly inhibited with anti-GM-CSF and anti-M-CSF antibodies, while CSA was inhibited by between 61 and 84%. We conclude that RA and VD3 synergistically inhibit the release of growth-enhancing substances by L1210 cells which may reduce the growth advantage of leukemic cells and the resulting leukocytosis in lymphocytic leukemia.
将L1210白血病细胞接种到受体小鼠体内后会发生类白血病反应，粒细胞增多的程度与肿瘤进展相关。研究发现，与正常小鼠血清相比，白血病小鼠血清中集落刺激活性（CSA）水平升高。L1210细胞体外培养条件培养基（L1210-CM）含有刺激正常骨髓髓系集落生长的CSA以及刺激L1210细胞增殖的自刺激活性（ASA）。我们研究了全反式维甲酸（RA）和1,25-二羟基维生素D3（VD3）对L1210细胞生长物质产生的影响。当在RA和VD3存在的情况下制备L1210-CM时，CSA和ASA受到明显抑制。两种药物联合使用比单独使用任何一种药物更有效。接种用任一种药物或两种药物联合处理的1×10⁵个L1210悬浮培养细胞的小鼠存活时间明显长于对照组。接种用两种药物联合处理的L1210细胞的小鼠存活时间最长。通过使用抗体，对L1210-CM中产生的生长物质进行的初步分析表明，它主要含有与ASA不同的粒细胞-巨噬细胞集落刺激因子（GM-CSF）和巨噬细胞集落刺激因子（M-CSF）样活性。联合抗体效价测定显示，抗GM-CSF和抗M-CSF抗体对ASA没有明显抑制作用，而CSA受到61%至84%的抑制。我们得出结论，RA和VD3协同抑制L1210细胞释放生长促进物质，这可能会降低白血病细胞的生长优势以及淋巴细胞白血病中由此导致的白细胞增多。
