The human leukemic myeloblast HL-60 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 cells. They are also a source of cytokines that affect other cell types.

Human leukemic models of myelomonocytic development: a review of the HL-60 and U937 cell lines.

In 1965 Wheelock reported that phytohemagglutinin could induce from human leukocytes an interferon-like virus inhibitor [1]. This substance, which turned out to be interferon-gamma (IFN-gamma), has been the subject, directly or indirectly, of thousands of scientific publications since that initial report. Past research has led to the general conclusion that IFN-gamma is much more than an interferon in that it has broader effects on the various arms of the immune system than most any other lymphokine or cytokine. In this review we discuss the effects of IFN-gamma on the various cell lineages of the immune system, focusing on the biology of its actions. In addition, we summarize research focused on the consequences of introducing IFN-gamma cDNA into tumor cells, aberrant IFN-gamma production in transgenic animals, and inhibition of IFN-gamma effects by knocking out either the IFN-gamma gene itself or the IFN-gamma receptor gene.

Role of interferon-gamma in immune cell regulation

Mitogenesis, cellular aggregation, and motility follow upon the interaction of fibrinogen with certain defined cell surface receptors In addition to circulating platelets and vascular endothelium, monocytes express what appears to be a receptor for fibrinogen Evidence is presented here that the leukocyte adhesion receptor Mac-1 can be specifically induced to bind fibrinogen with characteristics immunochemically and functionally distinct from the established Arg-Gly-Asp-directed fibrinogen receptors The competence of Mac-1 as a fibrinogen receptor is a general property of cells of monocyte and myeloid lineage acquired after maturational changes of some regions of the alpha subunit of Mac-1 during the process of cell differentiation This ligand recognition specificity of Mac-1 is lacking for the resting cell Rather, induction of fibrinogen binding capacity of Mac-1 is due to a cellular response to selected agonists characterized by inducing rapid transients of cytosolic Ca2+ Although different in activation pathways and recognition specificity, Mac-1 exhibits an oligospecific ligand versatility characteristic of other homologous Arg-Gly-Asp-directed adhesion receptors

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Oligospecificity of the Cellular Adhesion Receptor MAC-1 Encompasses an Inducible Recognition Specificity for Fibrinogen

Purification of a factor inducing differentiation of mouse myeloid leukemic M1 cells from conditioned medium of mouse fibroblast L929 cells.

The regulation of Mac-1, LFA-1, and p150,95 expression during leukocyte differentiation was examined. LFA-1 was present on almost all cell types studied. Both Mac-1 and p150,95 were present on the more mature cells of the myelomonocytic series, but only p150,95 was detected on some B cell lines and cloned cytotoxic T lymphocytes. Phorbol myristate acetate (PMA) stimulation of B chronic lymphocytic leukemia cells dramatically increased p150,95 expression. The resultant Mac-1, LFA-1, p150,95 phenotype resembled hairy cell leukemia, a B cell plasmacytoid leukemia. The promonocytic cell line U937 and the promyeloblastic cell line HL-60 expressed only LFA-1. Monocytic differentiation of U937 cells was stimulated by PMA, and induced the concomitant expression of Mac-1 and p150,95, with more p150,95 induced than Mac-1. Granulocyte/macrophage colony-stimulating factor (GM-CSF) stimulation of U937 cells gave similar results. PMA-stimulated monocytic differentiation of the HL-60 cell line also induced expression of both Mac-1 and p150,95. The number of p150,95 molecules on PMA-stimulated U937 and HL-60 cells were 5 X 10(5) and 3 X 10(5), respectively. Retinoic acid stimulated myeloid differentiation of HL-60 cells and induced expression of both Mac-1 and p150,95. These cells acquired a Mac-1, LFA-1, p150,95 profile that resembled that of granulocytes, with more Mac-1 than p150,95 induced. GM-CSF stimulation of HL-60 cells induced a similar Mac-1 and p150,95 phenotype. The contributions of Mac-1, LFA-1, and p150,95 to aggregation of PMA-differentiated U937 cells were assessed. Monoclonal antibodies to the beta subunit and the LFA-1 alpha subunit, but not those to p150,95 or Mac-1 alpha subunit, inhibited this homotypic adherence.

K. Welte

Papers

Lymphokine inducing "terminal differentiation" of the human monoblast leukemia line U937: a role for gamma interferon.

Leukemia Line U937: A Role for 'y Interferon