title: Distinct activities of interferon-gamma, lymphokine and cytokine differentiation-inducing factors acting on the human monoblastic leukemia cell line U937.
abstract: The human monoblast leukemia line U937 is growth inhibited and induced to express various characteristics of mature monocytes by lymphokines (LK) and other cytokines. Previous experiments have shown that interferon-gamma (IFN-gamma) is responsible for some but not all of the differentiation-inducing effects on U937. To determine the variety and specificity of activity, the following factors were studied: phytohemagglutinin-induced LK that contained IFN-gamma (100 units/ml); purified IFN-gamma; human colony-stimulating factor 1 (CSF-1); and conditioned medium(a) (CM) from the human bladder carcinoma cell line 5637 and the hepatoma cell line SK-HEP. LK preparations contained no colony-stimulating activity, whereas CM from 5637 and SK-HEP both contained granulocyte-macrophage CSF (3000 to 4000 units/ml) but no IFN activity. IFN-gamma is the major immunoglobulin G Fc receptor-inducing species within lymphokine, since anti-interferon-gamma antibody inhibited most of this activity. Other sources of Fc receptor-inducing activity were CM from SK-HEP and 5637 cell lines. Human CSF-1 when tested up to 800 units/ml was inactive for Fc receptor induction. LK induced the chemotactic peptide receptor, but this induction was due to factors other than IFN-gamma as anti-IFN-gamma antibody did not inhibit the induction, and purified IFN-gamma at a dose equivalent to that found in LK (100 units/ml) had no activity in the assay. SK-HEP and 5637 CM had strong chemotactic peptide receptor-inducing activity, but human CSF-1 was inactive up to 800 units/ml. Peroxide production after stimulation with phorbol myristic acid could be induced by LK, LK with anti-IFN-gamma antibody, 5637, and SK-HEP treatment. IFN-gamma (100 units/ml) and CSF-1 (800 units/ml) were ineffective. Peroxide production was induced by IFN-gamma at concentrations above 1000 units/ml. The inducibility of several enzymatic activities was determined as additional measures of maturation. N-Acetylglucuronidase was induced, for example, by LK, IFN-gamma, 5637 CM, and phorbol myristic acid. Alkaline phosphatase was induced by LK, IFN-gamma, dexamethasone, and phorbol myristic acid. 1,25-Dihydroxycholecalciferol was also examined and could induce most of the maturational markers examined. The results demonstrate that non-IFN cytokines from several sources have profound differentiation-inducing effects on monoblast leukemia cells in a pattern different from that of IFN-gamma.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.forename: P E
authors.initials: PE
authors.lastname: Harris
authors.forename: P
authors.initials: P
authors.lastname: Ralph
authors.forename: P
authors.initials: P
authors.lastname: Litcofsky
authors.forename: M A
authors.initials: MA
authors.lastname: Moore
mesh_terms: D000906:Antibodies; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D001688:Biological Products / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002630:Chemotactic Factors / Q000032:analysis; D016207:Cytokines; D006801:Humans; D006867:Hydrolases / Q000032:analysis; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D007948:Leukemia, Monocytic, Acute / Q000473:pathology*; D008222:Lymphokines / Q000494:pharmacology*; D009113:Muramidase / Q000032:analysis; D010587:Phagocytosis; D011961:Receptors, Fc / Q000032:analysis; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000032:analysis; D012397:Rosette Formation
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D001688:Biological Products; D002630:Chemotactic Factors; D016207:Cytokines; D008222:Lymphokines; D011961:Receptors, Fc; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D007371:Interferon-gamma; D006867:Hydrolases; D009113:Muramidase