Ikuta T, Honma Y, Okabe-Kado J, Kasukabe T, Hozumi M
Department of Chemotherapy, Saitama Cancer Center Research Institute, Japan.
Cancer Immunol Immunother. 1989;30(3):139-44. doi: 10.1007/BF01669421.
A growth-inhibitory (GI) factor, that specifically inhibits the growth of mouse monocytic leukemia cells, was found in conditioned medium of mouse lung tissue, but not in that of mouse brain, heart, liver, or kidney tissue. Conditioned medium of spleen or bone marrow cells had low GI activity. Pulmonary macrophages were as active as peritoneal and bone-marrow-derived macrophages in production of the GI activity. The GI factor inhibited the growth of murine monocytic leukemia cell lines Mm-A and J774.1, but scarcely inhibited the growth of other mouse cell lines, such as a myeloblastic leukemia cell line (M1), a Friend erythroleukemia cell line (745A) and a mammary carcinoma cell line (FM3A). It had no significant effect on the growth of human monocytic leukemia cell lines U937 and THP-1 or on the HL-60 promyelocytic leukemia cell line. These results suggest that the GI factor produced by mouse lung tissue preferentially inhibits the growth of mouse monocytic cells. The GI factor was found to be a proteinaceous substance with a molecular mass of 25 kDa. On chromatofocusing, the GI activity was eluted with Polybuffer 96/acetic acid at pH 7.2-7.5. The GI activity was not significantly decreased by heat treatment at 56 degrees C for 30 min or acid treatment (0.01 M HCl, 14 h), but the GI activity in glycosidase-treated conditioned medium of lung tissue was lost on heat treatment. The GI activity could not be neutralized with anti-(interferon alpha + beta) antibody. The activity was produced constitutively by lung tissues and its production was not stimulated appreciably by lipopolysaccharide, lectin, or poly(I).poly(C). The GI factor appears to be a cytokine unrelated to known cytokines such as tumor necrosis factor, interleukin-1, transforming growth factor beta, and interferons. These results suggest that the GI factor may be involved in negative feedback regulation of macrophage production in steady-state conditions in the lungs.
在小鼠肺组织的条件培养基中发现了一种生长抑制（GI）因子，它能特异性抑制小鼠单核细胞白血病细胞的生长，但在小鼠脑、心脏、肝脏或肾脏组织的条件培养基中未发现。脾脏或骨髓细胞的条件培养基具有较低的GI活性。肺巨噬细胞在产生GI活性方面与腹腔和骨髓来源的巨噬细胞一样活跃。GI因子抑制小鼠单核细胞白血病细胞系Mm - A和J774.1的生长，但几乎不抑制其他小鼠细胞系的生长，如成髓细胞白血病细胞系（M1）、弗氏红白血病细胞系（745A）和乳腺癌细胞系（FM3A）。它对人单核细胞白血病细胞系U937和THP - 1或HL - 60早幼粒细胞白血病细胞系的生长没有显著影响。这些结果表明，小鼠肺组织产生的GI因子优先抑制小鼠单核细胞的生长。发现GI因子是一种分子量为25 kDa的蛋白质物质。在色谱聚焦中，GI活性在pH 7.2 - 7.5的Polybuffer 96/乙酸中洗脱。在56℃热处理30分钟或酸处理（0.01 M HCl，14小时）后，GI活性没有显著降低，但经糖苷酶处理的肺组织条件培养基中的GI活性在热处理后丧失。GI活性不能被抗（干扰素α + β）抗体中和。该活性由肺组织组成性产生，其产生不受脂多糖、凝集素或聚（I）·聚（C）的明显刺激。GI因子似乎是一种与已知细胞因子如肿瘤坏死因子、白细胞介素 - 1、转化生长因子β和干扰素无关的细胞因子。这些结果表明，GI因子可能参与肺稳态条件下巨噬细胞产生的负反馈调节。
