Okubo A, Sone S, Tanaka M, Ogura T
3rd Department of Internal Medicine, University of Tokushima School of Medicine, Japan.
Cancer Res. 1989 Jan 15;49(2):265-70.
Human blood monocytes isolated by centrifugal elutriation from healthy donors were tested for ability to produce membrane-associated antitumor monokine(s) in response to activation stimuli such as various types of interferon (IFN) and/or synthetic desmethyl muramyl dipeptide (norMDP). IFNs (alpha, beta, and gamma) and norMDP rendered blood monocytes cytotoxic to allogeneic A375 melanoma cells, as assayed by measuring release of [125I]iododeoxyuridine in 72 h. When monocytes were treated with any type of IFN for 16 h, and then fixed with paraformaldehyde, they did not show cytotoxicity to A375 cells, but when they were fixed after treatment with norMDP or lipopolysaccharide they showed significant cytotoxicity to A375 melanoma cells. This membrane-associated antitumor monokine induced by the synergistic actions of suboptimal concentrations of IFN-gamma and norMDP, was cytotoxic to HT-29 colon cancer cells as well as A375 melanoma cells, but not to actinomycin D-treated L-929 cells. The fixed monocyte-mediated cytotoxicity against A375 melanoma cells was completely inhibited by a specific anti-interleukin 1 alpha antiserum, but not by a specific anti-interleukin 1 beta antiserum or monoclonal anti-TNF antibody. These results suggest that membrane-associated interleukin 1 alpha is involved through cell-to-cell contact in the host defense mechanism against cancer.
从健康供体通过离心淘析分离出的人血单核细胞，检测其在诸如各种类型的干扰素（IFN）和/或合成去甲酰化胞壁酰二肽（norMDP）等激活刺激下产生膜相关抗肿瘤单核因子的能力。通过在72小时内测量[125I]碘脱氧尿苷的释放来检测，IFN（α、β和γ）和norMDP使血单核细胞对同种异体A375黑色素瘤细胞具有细胞毒性。当单核细胞用任何一种IFN处理16小时，然后用多聚甲醛固定时，它们对A375细胞没有显示出细胞毒性，但当它们在用norMDP或脂多糖处理后固定时，它们对A375黑色素瘤细胞显示出显著的细胞毒性。由次优浓度的IFN-γ和norMDP的协同作用诱导的这种膜相关抗肿瘤单核因子，对HT-29结肠癌细胞以及A375黑色素瘤细胞具有细胞毒性，但对放线菌素D处理的L-929细胞没有细胞毒性。固定的单核细胞介导的对A375黑色素瘤细胞的细胞毒性被特异性抗白细胞介素1α抗血清完全抑制，但不被特异性抗白细胞介素1β抗血清或单克隆抗TNF抗体抑制。这些结果表明，膜相关白细胞介素1α通过细胞间接触参与宿主抗癌防御机制。
