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Separation of different molecular forms of macrophage- and granulocyte-inducing proteins for normal and leukemic myeloid cells. 1980

J Lotem, and J H Lipton, and L Sachs
Department of Genetics, Weizmann Institute of Science, Rehovoth, Israel.

It is shown that serum of mice treated with endotoxin (ES) contains three separable and functionally distinct forms of macrophage- and granulocyte-inducing (MGI) proteins. One form (MGI-1M) induced the formation of macrophage colonies from normal bone-marrow cells and showed on gel filtration an apparent molecular weight of 300,000; a second form (MGI-1G) induced the formation of granulocyte colonies from normal bone-marrow cells and had an apparent molecular weight of 45-100,000; and the third form (MGI-2) induced the normal differentiation of MGI+D+ myeloid leukemic cells to macrophages and granulocytes and had an apparent molecular weight of 28,000. Studies on the time course of the decrease of these three activities in ES have indicated that MGI-2 was more readily inactivated in vivo than MGI-1M and MGI-1G. The MGI-1M in ES isolated after gel filtration was completely neutralized by an antiserum to MGI-1 from mouse L-cells, whereas the isolated MGI-1G and MGI-2 were not affected by this antiserum. Gel filtration under dissociating conditions (6 M guanidinium chloride) resulted in a reduction of the apparent molecular weights of MGI-1M from 300,000 to 42,000, and of MGI-1G from 45-100,000 to 28,000, while it produced no change in the 28,000 apparent molecular weight of MGI-2. Similar studies with conditioned medium produced in vitro from mouse lung and peritoneal macrophages showed that in these conditioned media, MGI-1 (both G and M) in the native form had an apparent molecular weight of 41,000 and MGI-2 of 24,000, and that both MGI-1 and 2 had an apparent molecular weight of 24,000 under dissociating conditions. The results indicate that MGI-1 exists in serum in vivo and in these conditioned media as aggregated proteins, whereas MGI-2 does not, and that macrophages and lung tissue are not the only source of the MGI proteins found in ES. It is suggested that all three forms of MGI activity are derived from one precursor protein; that only the MGI-2 form assayed on leukemic cells should be used for treatment based on the induction of normal cell differentiation in myeloid leukemia; and that MGI-2 may serve as a survey mechanism for inducing differentiation in myeloid leukemic cells that have lost their responsiveness to the MGI-1 molecules that control the viability, proliferation and differentiation of normal myeloblasts.

UI MeSH Term Description Entries
D007942 Leukemia, Experimental Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues. Experimental Leukemia,Experimental Leukemias,Leukemia Model, Animal,Leukemias, Experimental,Animal Leukemia Model,Animal Leukemia Models,Leukemia Models, Animal
D007951 Leukemia, Myeloid Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites. Granulocytic Leukemia,Leukemia, Granulocytic,Leukemia, Myelocytic,Leukemia, Myelogenous,Myelocytic Leukemia,Myelogenous Leukemia,Myeloid Leukemia,Leukemia, Monocytic, Chronic,Monocytic Leukemia, Chronic,Chronic Monocytic Leukemia,Chronic Monocytic Leukemias,Granulocytic Leukemias,Leukemia, Chronic Monocytic,Leukemias, Chronic Monocytic,Leukemias, Granulocytic,Leukemias, Myelocytic,Leukemias, Myelogenous,Leukemias, Myeloid,Monocytic Leukemias, Chronic,Myelocytic Leukemias,Myelogenous Leukemias,Myeloid Leukemias
D012016 Reference Values The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016178 Granulocyte-Macrophage Colony-Stimulating Factor An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. CSF-GM,Colony-Stimulating Factor, Granulocyte-Macrophage,GM-CSF,Histamine-Producing Cell-Stimulating Factor,CSF-2,TC-GM-CSF,Tumor-Cell Human GM Colony-Stimulating Factor,Cell-Stimulating Factor, Histamine-Producing,Colony Stimulating Factor, Granulocyte Macrophage,Granulocyte Macrophage Colony Stimulating Factor,Histamine Producing Cell Stimulating Factor,Tumor Cell Human GM Colony Stimulating Factor
D016179 Granulocyte Colony-Stimulating Factor A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. Colony-Stimulating Factor, Granulocyte,G-CSF,Myeloid Growth Factor,Colony Stimulating Factor, Granulocyte,Factor, Granulocyte Colony-Stimulating,Factor, Myeloid Growth,Granulocyte Colony Stimulating Factor,Growth Factor, Myeloid
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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