Inhibition of differentiation and affinity purification with a monoclonal antibody to a myeloid cell differentiation-inducing protein.
The normal myeloid hematopoietic regulatory proteins include four growth-inducing proteins called colony-stimulating factors (CSF), including interleukin-3 (IL-3), or macrophage and granulocyte inducers, type 1 (MGI-1), and another type of protein (MGI-2) with no myeloid cell growth-inducing activity that induces differentiation of normal myeloid precursor cells and certain clones of myeloid leukemic cells. An IgG2a monoclonal antibody was prepared and it neutralized two forms of MGI-2 (MGI-2A and MGI-2B) produced by mouse Krebs ascites tumor cells. The monoclonal antibody was used for affinity purification of MGI-2. This antibody also neutralized MGI-2 produced by normal mouse macrophages, normal myeloblasts incubated with IL-3, and MGI-2 produced by the lungs and found in the serum of mice injected with lipopolysaccharide (LPS). The anti-MGI-2 antibody did not inhibit the activity of any one of the four myeloid growth-inducing proteins (CSF or IL-3 = MGI-1), IL-1, tumor necrosis factor, or lymphotoxin. This antibody also inhibited induction of differentiation of myeloid leukemic cells by LPS, which is mediated by the endogenous production of MGI-2, but did not inhibit induction of differentiation in these leukemic cells by dexamethasone or cytosine arabinoside, which is not mediated by MGI-2. Anti-MGI-2 antibody thus inhibited differentiation when MGI-2 was added externally to cells or when it was mediated by endogenously produced MGI-2.
Shabo
Y
Y
Department of Genetics, Weizmann Institute of Science, Rehovot, Israel.
Sachs
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002846:Chromatography, Affinity; D003115:Colony-Stimulating Factors / Q000502:physiology; D003561:Cytarabine / Q000037:antagonists & inhibitors; D003907:Dexamethasone / Q000037:antagonists & inhibitors; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006131:Growth Inhibitors; D006133:Growth Substances / Q000502:physiology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D007163:Immunosorbent Techniques; D007377:Interleukin-3 / Q000502:physiology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000302:isolation & purification*; D051379:Mice; D008970:Molecular Weight; D009500:Neutralization Tests
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D006131:Growth Inhibitors; D006133:Growth Substances; D007377:Interleukin-3; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008070:Lipopolysaccharides; D008222:Lymphokines; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor