Cozzolino F, Rubartelli A, Aldinucci D, Sitia R, Torcia M, Shaw A, Di Guglielmo R
Istituto di Clinica Medica IV, Università di Firenze, Italy.
Proc Natl Acad Sci U S A. 1989 Apr;86(7):2369-73. doi: 10.1073/pnas.86.7.2369.
Production of interleukin 1 (IL-1) by leukemic cells was studied in 13 cases of acute myeloid leukemia. Intracytoplasmic immunofluorescence studies showed that the cells invariably contained the cytokine. Endogenous labeling studies demonstrated that acute myeloid leukemia cells produced either only the 33-kDa propeptide or both the propeptide and the 17-kDa mature form of IL-1 beta. The 33-kDa propeptide IL-1 alpha was always produced but was less frequently released. Involvement of IL-1 in leukemic cell growth was investigated using two antibodies specific for IL-1 subtypes, which inhibited spontaneous cell proliferation in the six cases studied. After acid treatment of the cells, a surface receptor for IL-1 could be demonstrated, which mediated 125I-labeled IL-1-specific uptake by leukemic cells. Furthermore, recombinant IL-1 alpha or IL-1 beta induced significant cell proliferation in 10 of 12 cases. The above findings were uncorrelated with the cytologic type (French-American-British classification) of leukemia. Our studies suggest that IL-1 may act as an autocrine growth factor in most cases of acute myeloid leukemia.
对13例急性髓性白血病患者的白血病细胞产生白细胞介素1(IL-1)的情况进行了研究。胞浆内免疫荧光研究显示,这些细胞均含有该细胞因子。内源性标记研究表明,急性髓性白血病细胞要么仅产生33 kDa的前体肽,要么同时产生前体肽和17 kDa的成熟形式的IL-1β。33 kDa的前体肽IL-1α总是会产生,但释放频率较低。使用两种针对IL-1亚型的特异性抗体研究了IL-1在白血病细胞生长中的作用,这两种抗体在所研究的6例患者中抑制了自发细胞增殖。对细胞进行酸处理后,可证明存在IL-1的表面受体,该受体介导白血病细胞对125I标记的IL-1的特异性摄取。此外,重组IL-1α或IL-1β在12例中的10例中诱导了显著的细胞增殖。上述发现与白血病的细胞学类型(法美英分类)无关。我们的研究表明,在大多数急性髓性白血病病例中,IL-1可能作为一种自分泌生长因子发挥作用。