Abstract We have utilized the U937 macrophage cell line as a model system for analysis of human mononuclear phagocyte (MNP) differentiation. In addition to expressing membrane antigens shared with other MNP, U937 possesses an intrinsic ability to become “activated” upon exposure to lymphokines. A heteroantiserum produced against lymphokine-stimulated U937 (anti-U937L) was utilized to detect acquired or inducible membrane antigens expressed on “activated” U937. Absorption of this antiserum to remove antibodies to nonstimulated U937 (U937N) did not remove the reactivity of anti-U937L/U937N to lymphokine-stimulated U937 as determined by an 125 I-protein A radioimmunoassay. The lymphokine-inducible antigens were not detectable on resident, human peritoneal macrophages. In addition to expression of lymphokine-inducible antigens, treated U937 cells displayed alterations in both morphology and functional activity (antibody-dependent cellular cytotoxicity). Kinetic analysis of lymphokine-stimulated U937 indicated that antigen expression occurred as early as 1–2 hr after lymphokine exposure, plateauing at 16–18 hr of stimulation. The inducible antigens were susceptible to proteolytic degradation and expression was blocked by inhibitors of protein synthesis. Inducible antigens detectable by anti-U937L/U937N did not result from the expression of cryptic or buried membrane antigens. Thus, the U937 cell line can be utilized for production of antibodies useful in analysis of membrane antigen expression during differentiation within the MNP system.
SUMMARY An alloantiserum has been obtained in the mouse which differentiates specifically between lymph node cells and a sub-population of peritoneal cells. The antigen is associated with chromosome 7 (linkage group I).
The phenotype of three ectoenzymes was determined for murine resident peritoneal macrophages, macrophages elicited in vivo by treatment of mice with thioglycollate, Corynebacterium parvum or pyran, and for resident macrophages activated in vitro by treatment with lymphokine. The relationship of these biochemical markers to macrophage antiviral and anti-tumor activity was established. Thioglycollate-elicited macrophages showed a unique ectoenzyme phenotype, with increased leucine aminopeptidase a...
When cells of human macrophage-like cell line U937 are cultured in the presence of medium conditioned by mixed lymphocyte culture (MLC), PHA- or Con A-stimulated lymphocytes they demonstrate morphologic and functional characteristics of stimulation. The cells become larger, their surface more villous, and the cytoplasm has increased numbers of lysosomes and phagosomes. There is a marked (at least 10-fold) increase in antibody-dependent cellular cytotoxicity (ADCC) against both erythroid and tumo...
A human monocyte-like cell line, U937, when grown in continuous culture, does not secrete lysosomal enzymes or migrate towards chemotactic factors. When the cells are stimulated by lymphokines, however, they develop the ability both to migrate directionally and to secrete enzymes in response to several types of chemoattractants. The development, by stimulated cells, of chemotactic and secretory responses to one class of chemoattractants, the N- formylated peptides, is accompanied by the appearan...
#1Kwok-Choy Lee(U of A: University of Alberta)H-Index: 15
Functionally distinct subpopulations of macrophages at various stages of differentiation can be separated by fractionation of murine peritoneal cells according to size, since the maturation of monocytes into macrophages is associated with cell enlargement. For immunostimulatory functions which can be served by macrophage-derived factors, normal macrophages of all sizes will function very well. However, in the antigen-specific T cell proliferative response which requires the presentation of antig...
Thymic adherent cells were isolated after their enrichment on density gradients. The predominant cell type found was the macrophage, as determined by morphology, surface receptors for Fc and C3, phagocytosis and esterase activity. There was, in addition, a minor fraction of cells with a distinctive dendritic morphology. These dendritic cells had surface properties similar to macrophages but limited phagocytic capacity. Approximately 50% of thymic adherent cells bear Ia antigens detected by immun...
Studies of the binding of monomeric murine IgG2a and IgG2b to the macrophage-like cell line P388D1 confirmed the existence of at least two classes of Fc receptors. One receptor binds IgG2a preferentially, whereas the second interacts better with IgG2b. Approximately equal numbers of each class of receptor were present. The receptors showed a marked cross-specificity toward IgG2 subclass proteins but did not recognize murine IgG1. The P388D1 receptors were used to study the phylogenetic emergence...
Antisera produced in rabbits against adherent cells of rat alveolar or peritoneal lavage fluid (anti-rat alveolar macrophage sera, ARAMS, or anti-rat peritoneal macrophage sera, ARPMS) were used to detect antigenic differences between alveolar (AM) and peritoneal (PM) macrophages in an indirect membrane immunofluorescence (IMF) test. Of all sera tested, the IMF titres were higher with cells of that population which was used for immunization. These differences were found before and after exhausti...
Monocytes were isolated by counterflow centrifugation of Ficoll-Hypaque separated peripheral blood mononuclear cells. The monocytes formed a bimodal volume distribution of “large” and “small” phagocytic esterase-positive, peroxidase-positive cells with peaks at 470 and 410 µ3, respectively. The large monocytes were predominately Fc receptor positive, and were able to lyse both sensitized human and chicken erythrocyte targets in ADCC assays, whereas the small monocytes were largely FcR negative a...
Dipeptidyl peptidase-4 (DPP-4 or CD26) inhibitors, a new class of anti-diabetic compounds, are effective in treatment of hyperglycemia. Since atherosclerosis-related cardiovascular diseases are the major complications of diabetes, it is important to determine the effect of DPP-4 inhibitors on atherosclerosis. In this study, nondiabetic and diabetic apolipoprotein E (apoE)-deficient mice were treated with DPP-4 inhibitor alogliptin for 24 weeks and atherosclerotic lesions in aortic origins were e...
A major component of innate immune responses relies on monocytes and macrophages, virus infection of which will pose a particular problem for immunological defense. Consequently, the monocytic cell differentiation pathway was analyzed in terms of cellular modulations therein and their relation to monocytotropic virus infection. Differentiation was characterized by down-regulation of CD14, MHC Ags, the monocytic SWC1 marker, and p53; concomitant up-regulation of the SWC9 macrophage marker, a puta...
Monocytes were prepared from human blood and allowed to differentiate into macrophages in vitro. Synthesis and secretion of the potent proteinase inhibitor α2-macroglobulin is strongly induced during maturation of monocytes into macrophages establishing α2-macroglobulin as a differentiation marker protein. When the monocytes were incubated with endotoxin (S. typhi) in a concentration as low as 100 ng/ml, induction of α2-macroglobulin synthesis was completely abolished indicating impaired monocyt...
The Induction of differentiation in the human monoblastlike cell line U937 by 1,25 dihydroxyvitamln 03, interferon gamma, or phorbol esters is associated with the expression of a novel surface antigen, 7C3. The expression of 7C3 is maximal after 24 hr and is dependent upon de novo protein synthesis. The appearance of 7C3 during U937 differentiation is inhibited by dexamethasone while the increased expression of the macrophage marker OKM1 is not affected. 7C3 antigen is also expressed on HL6O cel...
#2Joji Notani(Loyola University Medical Center)H-Index: 1
Last. Jun Minowada(Loyola University Medical Center)H-Index: 10
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Abstract A panel of human leukemia cell lines from various lineages (T-cell, pre B- and Non-T/Non-B cell, myelomonocytic and erythroleukemia cell lines) were utilised as model systems of the distinct effects of differentiation-inducing activity (DIA) produced by the T-leukemia cell line HUT-102. DIA inhibited cell proliferation and induced distinct morphological changes which were more pronounced in the myelomonocytic and erythroleukemia cell lines than in the lymphoid cell lines. DIA triggered ...
Abstract Recombinant human immune interferon (HuIFN-gamma) was labeled with [gamma-32P]ATP and cyclic-AMP-dependent protein kinase from bovine heart to a specific radioactivity of 11,000 Ci/mmol. At least two molecules of phosphate were incorporated per molecule of interferon. The binding of [32P]HuIFN-gamma to human U937 histiocytic lymphoma cells was time dependent, and displaceable by HuIFN-gamma but not by HuIFN-alpha A or HuIFN-beta. The specific binding was saturable with less than 10% non...
#1Paul E. Harris(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 37
#1Paul L. Harris(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 99
Last. Peter Ralph(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 35
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The human leukemic myeloblast HL-6O and monoblast U937 cell lines have made important contributions to the disciplines of cancer, hematology, and immunology. As sources of leukemic cells, they have been used for the study of neoplasia and therapeutics. As sources of hemic cells, they have been used for biochemical and biological analysis of regulation and differentiation in myelopoiesis. When stimulated with immunomodulatory factors, the cell lines develop properties of host-defense effector cel...
• The pathogenesis of chronic idiopathic uveitis is not known. Analysis of inflammatory site (ie, intraocular) lymphocytes in the aqueous humor and/or vitreous cavity was performed with monoclonal antibodies and a cell sorter. The mononuclear cell population within the aqueous humor of eyes with acute idiopathic uveitis resembled that observed in the peripheral blood. In contrast, eyes with chronic idiopathic uveitis displayed a scarcity of T cells within the vitreous. Eyes with chronic uveitis ...
The human monoblast leukemia line, U937, is growth-inhibited and induced to develop markers of mature monocytes by lymphokine preparations. Lymphokine is cytostatic and induces expression of Fc receptors in U937 and in myelomonocytic leukemic lines RC-2A and KG-1, but does not have these effects on T- and B-lymphocytic lines. In addition to previously described properties, including complement receptors, phagocytosis, and antibody-dependent cellular cytotoxicity (ADCC), Mac-1 and Mac-3 surface a...