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Biomedical subjects

F Dianzani

Publications and source records attributed to F Dianzani.

At least 127 records · Page 7Linked to original sources
PubMed1986

A new type of human interferon produced by peripheral blood mononuclear cells treated with inhibitors of transcription.

Peripheral blood mononuclear cells from human normal donors treated with inhibitors of transcription produce a protein with the properties of interferon (IFN) [activity against a broad range of viruses, species specificity, lack of blockade of virus attachment, capability to induce in cells durable antiviral state, establishment of antiviral state requiring ongoing protein and RNA synthesis, capability to induce 2',5'-oligoadenylate synthetase]. This IFN-like protein has a molecular weight of approximately 7000 daltons and is not neutralized by antibody to alpha-, beta-, and gamma-IFNs tested singularly or in a pooled fashion. Taken together the data suggest that this IFN-like protein may indeed be a new type of human IFN.

2',5'-Oligoadenylate Synthetase↗
PubMed1986

Antigen presentation by specifically sensitized macrophages in interferon-gamma induction.

Antigenic stimulation of specifically sensitized T lymphocytes to interferon-gamma (IFN-gamma) production requires the presence of macrophages. This study examines the ability of peritoneal macrophages from immunized mice to present the antigen to antigen-specific lymphocytes. Such cells presented purified protein derivative (PPD) of tuberculin at concentrations as low as 0.1 micrograms/ml to sensitized T lymphocytes. In contrast, peritoneal macrophages from unimmunized animals required 1,000-fold higher concentrations of antigen to stimulate the same lymphocytes. The presentation of low concentrations of antigen by macrophage from immunized animals was significantly blocked by anti-immunoglobulin antibody, indicating that the surface immunoglobulin receptors were critically involved in this phenomenon. These results suggest that surface immunoglobulins serve to focus antigens onto specific macrophages and that such cells are highly efficient at presenting linked antigenic determinants to T cells. The implication of these findings for the mechanism of IFN-gamma induction are discussed.

Animals↗
PubMed1986

Direct and cell-mediated effects of interferon-alpha and -gamma on cells chronically infected with HTLV-III.

The replication of the human T lymphotropic retrovirus HTLV-III in persistently infected cells is relatively insensitive to the direct antiviral action of human interferon-alpha or -gamma (IFN-alpha or -gamma), showing only a two- to threefold reduction of HTLV-III, even though the host cells are very sensitive to IFN, as shown by vesicular stomatitis virus (VSV)-yield reduction assay (4-5 log reduction of VSV). However, IFN anticellular activity is strongly enhanced in the presence of normal peripheral blood mononuclear cells, suggesting a cell-mediated effect of IFNs.

Acquired Immunodeficiency Syndrome↗
PubMed1986

An influenza virus inhibitor that acts late in the replication cycle.

An inhibitor which is active against influenza A virus was found in Neuramide, a complex tissue extract that is used as an anti-herpes zoster virus treatment. Kinetic studies showed that significant inhibition of virus production occurred when the inhibitor was added to infected cultures up to 5 h after virus penetration. Molecular sieving fractionation showed that the antiviral activity was contained in a low-molecular-weight fraction (molecular weight, less than 1,000).

Animals↗
PubMed1986

Effects of dexamethasone on human natural killer cell cytotoxicity, interferon production, and interleukin-2 receptor expression induced by microbial antigens.

Dexamethasone inhibits the expression of the interleukin-2 receptor, the synthesis of immune interferon, and the development of natural killer cells when added to peripheral blood mononuclear cells cultured with soluble microbial antigens (purified protein derivative and a polysaccharide extract from Candida albicans [MPPS]) or human recombinant interleukin-2.

Antigens, Bacterial↗
PubMed1986

Regulation of immune interferon production during the response to soluble microbial antigens.

Human peripheral blood mononuclear cells (PBMC) stimulated in vitro with purified protein derivative (PPD) or with a Candida albicans polysaccharide extract (MPPS) released immune interferon (IFN) and interleukin 2 (IL-2). Kinetic studies showed a biphasic production of IFN with maximum levels at days 3-4 and days 5-6 of culture. In contrast, the IL-2 production is only observed at days 2-3 of culture. The relationship between IFN and IL-2, analysed both in responder and nonresponder PBMC cultures, showed that the early peak of IFN production appears to be IL-2 independent whereas the second peak seems strictly related to the presence of IL-2 culture. Furthermore, monoclonal antibodies against class I and class II products of the major histocompatibility complex (MHC) inhibited IFN production when added at the beginning of culture, whereas only anti-class I antibodies interfered with the release of IFN when added to antigen-primed lymphocytes.

Adult↗
PubMed1985

Generation of a soluble IFN-gamma inducer by oxidation of galactose residues on macrophages.

Depletion of macrophages from human peripheral blood mononuclear cells (PBMC) caused a marked decrease in galactose oxidase and sodium periodate, but not a calcium ionophore, stimulated Interferon-gamma (IFN-gamma) production. Reconstitution of such depleted cultures with galactose oxidase treated macrophages, but not lymphocytes, restored IFN-gamma levels to those of control nonfractionated PBMC. Thus, galactose oxidase seemed to act on macrophages which in turn stimulated lymphocyte production of IFN-gamma. Unlike human cells which have terminal galactose residues on glycoproteins, murine cell glycoproteins terminate their oligosaccharide component in the order N-acetyl-neuraminic acid followed by D-galactose, N-acetyl-glucosamine, and glycoprotein. Galactose oxidase or sodium periodate only activated murine macrophages to stimulate lymphocyte IFN-gamma production after exposing D-galactose residues by the removal of the terminal N-acetyl-neuraminic acid residues with neuraminidase. Removal of such exposed terminal galactose residues with beta-galactosidase inhibited the effect of galactose oxidase on murine macrophages. Taken together, these results strongly suggest that oxidation of terminal galactose residues on macrophages is the initial site of action of galactose oxidase and sodium periodate. Studies with Boyden chambers have shown that galactose oxidase-treated macrophages released a soluble factor which stimulates lymphocyte production of IFN-gamma. Based on these findings, it appears that the oxidation of terminal galactose residues on the surface of macrophages leads to the induction and transmission of a soluble signal for lymphocyte production of IFN-gamma.

Animals↗
PubMed1985

Impaired gamma interferon production by cells from patients with lymphoproliferative disorders of mature T and NK cells.

We investigated interferon (IFN) production by peripheral blood mononuclear cells from four patients with chronic OKT4 T-lymphocytic leukaemia and three patients with abnormal expansions of granular lymphocytes. No spontaneous production of IFN-gamma was found in supernatants of cultures from both patients and normal controls. However, whereas the enzyme galactose oxidase or staphylococcal enterotoxin B was able to induce IFN-gamma production by normal cells, no production could be obtained in the cells under study. The possibility that this lack of production might have been attributed to an excess of N-acetylneuraminic acid masking galactose residues or to a defect of monocyte accessory cells was ruled out either by pre-treating the cells with neuraminidase or by adding normal adherent cells to the cultures, both of which resulted in a lack of production. On the contrary, the calcium ionophore A23187 (considered to act as a second specific step, following oxidation of galactose residues, toward genetic derepression of IFN-gamma) induced considerable IFN-gamma production in all the three tested patients. It can be concluded that, although in rare cases, as previously reported by other authors, cells from patients with T or NK lymphoproliferative disorders may spontaneously produce IFN-gamma, this is not a general mechanism that underlies the disease. In fact, in all our cases a defect of IFN-gamma production was found. This defect seems due to an alteration at the membrane level of the galactose-containing glycoproteins and can be restored by induction with a calcium ionophore.

Adult↗
PubMed1985

Group B coxsackieviruses readily establish persistent infections in human lymphoid cell lines.

Exposing human lymphoid cell lines to uncloned or recently cloned group B coxsackieviruses results in the frequent establishment of chronically infected cultures. Persistence is maintained by a carrier culture mechanism involving virus spread through the medium and replication among a minority of cells at any given time. These studies provide a model for persistence by highly cytocidal viruses.

Cell Line↗
PubMed1985

Membrane events leading to interferon-gamma induction by antigens.

Mitogenic induction of interferon-gamma in human peripheral blood mononuclear cells (PBMC) is prevented by enzymatic cleavage of galactose residues on the cell membrane, and by calcium depletion, suggesting that oxidation of galactose on the membrane glycoproteins and activation of a calcium flux across the membrane are critical events for interferon-gamma induction in nonspecifically stimulated human PBMC. The same experimental design has been applied to human PBMC cultures enriched of specifically sensitized lymphocytes and stimulated with the respective antigens. The results of these experiments show that also antigenic induction of interferon-gamma by purified protein derivative, tetanus toxoid, and MLR requires integrity of galactose residues and calcium intake suggesting that alteration of membrane-bound galactose and activation of a calcium flow are critical triggering events for both specific and nonspecific lymphocyte activation.

Adult↗
PubMed1985

Induction of alpha interferon by membrane interaction between viral surface and peripheral blood mononuclear cells.

Cells infected with viruses and fixed when viral antigens appeared at the cell membrane induced much higher alpha interferon (IFN-alpha) levels in human peripheral blood mononuclear cells (PBMC) than free virions. Relatively few inducer cells were sufficient for triggering IFN production. Optimal IFN yields depended on inducer/producer cell ratio. The response was peculiar to PBMC as it was not found in other cells in which IFN can normally be induced by free virions. IFN inducing activity was also exerted by live virus-infected PBMC, showing that this type of induction may have physiological importance. These findings confirm that viral induction of IFN-alpha is activated by some interaction between viral components presented at the cell surface and PBMC membrane. Thus induction of IFN by circulating cells infected by viruses and presenting viral antigens at the surface may be an efficient host defense mechanism. Since IFN yields close to 10(6) international units per milliliter are obtained, this system has potential for large scale production of native IFN-alpha.

Animals↗
PubMed1984

Interferon production in primary immunodeficiencies.

Alpha- and gamma-interferon (IFN) production by peripheral blood mononuclear cells (PBMC) from 18 patients affected by primary immunodeficiency syndromes was examined and compared with that of 20 normal donors. Patients included 8 with common variable immunodeficiency (CVI), 2 with congenital agammaglobulinemia, 4 with ataxia-telangiectasia, 2 with hyper-IgE syndrome, 1 with chronic EBV infection, 1 with combined immunodeficiency, and 1 with immunodeficiency with hyper-IgM. No spontaneous IFN production was observed in either patients and controls. Newcastle disease virus-induced alpha-IFN production was found to be normal in all patients. Gamma-IFN was induced by both galactose oxidase and staphylococcal enterotoxin (B). Gamma-interferon production was low or undetectable in patients with ataxia-telangiectasia, in immunodeficiency with hyper-IgM, and in hyper-IgE syndrome. No major defect of gamma-IFN was found in other types of immunodeficiency, despite the presence of occasional low producers (1 of 8 CVI patients and 1 case of congenital agammaglobulinemia). No correlation was found between IFN production and natural killer activity in individual patients. The analysis of lymphocyte subsets by monoclonal antibodies revealed gross imbalances of helper/inducer and suppressor/cytotoxic subpopulations, but no overall correlation could be established with gamma-IFN production. The observation of major defects in gamma-IFN yield only in diseases with depression of T cell-mediated immunity might contribute to a better understanding of the pathogenetical mechanisms in these diseases. Moreover, future studies should monitor these in vitro functions and their modifications by in vitro or in vivo manipulations.

Adolescent↗
PubMed1984

Defective interferon-gamma production in ataxia-telangiectasia.

The in vitro production of interferon-alpha and -gamma (IFN) by peripheral blood mononuclear cells from four patients with ataxia-telangiectasia was compared to that of healthy controls. Normal values of IFN-alpha were obtained in all cases. However, patients with ataxia-telangiectasia showed a great reduction or absence of IFN-gamma production after induction with either staphylococcal enterotoxin B or galactose oxidase. This defect was accompanied by the absence of secretion of another lymphokine, namely, interleukin 2 (IL-2), in one case. Lymphoproliferative response to phytohemagglutinin (PHA) was severely depressed in all patients. Near normal values of T lymphocytes were found, but the ratio of OKT4+/OKT8+ subsets was reduced in most patients, due to a decrease of OKT4+ lymphocytes. Deficiency of IFN-gamma may contribute to the abnormalities of immune functions and immunoregulation observed in ataxia-telangiectasia, and it may represent an additional cause of the high incidence of viral infections and neoplasia in this disease.

Adolescent↗
PubMed1984

Role of calcium in gamma interferon induction: inhibition by calcium entry blockers.

Mitogen-induced gamma interferon production by human lymphoid cell cultures was studied in the presence of calcium entry blockers. A dose-dependent inhibition was found in the presence of drug concentrations down to 10(-5) M. This finding shows that calcium flow through lymphocyte membranes after oxidation of membrane-bound galactose residues is also critical for triggering interferon production.

Calcium↗
PubMed1983

Immune (gamma) interferon production by a murine T cell lymphoma: requirements for macromolecular synthesis and lack of relationship with cell cycle.

Macromolecular synthesis of immune interferon (IFN-gamma) by the L12-R4 T cell lymphoma, stimulated by phorbol myristic acetate, was studied by using reversible inhibitors of protein synthesis, puromycin and cycloheximide, and an irreversible inhibitor of RNA synthesis, actinomycin D. Reversible inhibition of protein synthesis during the first 3 h of stimulation had no effect on IFN-gamma production. The same treatment, performed 4 h after stimulation and maintained for an additional 5 h, decreased significantly the capability of L12-R4 cells to produce IFN-gamma. When the inhibitors of protein synthesis were left in the cultures, a complete block of IFN-gamma production was observed. Irreversible inhibitors of RNA synthesis at the beginning of stimulation did block IFN-gamma production by L12-R4 cells, but the same treatment was ineffective if performed 6 h after stimulation. These data suggest that continued protein synthesis is needed for IFN-gamma production, whereas the RNA seems to be completely synthesized within 4 to 6 h of stimulation. The relationship between IFN-gamma production and cell cycle phases was studied with the aid of a reversible drug, aphidicolin, that arrests cells at the G1/S border. Phorbol myristic acetate stimulation of L12-R4 cells after aphidicolin removal induced comparable levels of IFN-gamma at each different point of stimulation, indicating that IFN-gamma production by stimulated cells is not related to a particular phase but is continuously inducible during the cell cycle.

Animals↗
PubMed1983

Ocular herpes simplex virus infection is diminished by depletion of B lymphocytes.

Rabbit anti-mouse mu-chain serum was used to deplete specifically IgM-bearing B cells and B cell function in BALB/c mice. B cell-depleted and normal littermates were infected via the cornea with herpes simplex virus type 1 (HSV-1) at 4 to 5 wk of age. B cell-depleted mice had a reduced number of lymphocytes bearing surface immunoglobulin and a greatly reduced ability to produce antibody. Mortality was reduced from 89% in normal controls to 42% in B cell-depleted mice (p less than 0.001) and peak virus shedding from eyes was also reduced as much as 90% in the B cell-depleted mice (p less than or equal to 0.0005). These results support the hypothesis that a B cell function of normal mice somehow contributes directly or indirectly to the enhanced mortality of mice infected with HSV.

Animals↗
PubMed1982

Membrane alteration responsible for the induction of gamma interferon.

Induction of gamma interferon in human lymphoid cells cultures appears to be dependent upon specific membrane-mediated events and calcium flux. Since blastic response had been observed after enzymic oxidation of membrane-bound galactose residues, we used this system to study the nature of membrane alterations responsible for the activation of interferon induction. The results of these experiments suggest that a membrane oxidation is essential for interferon induction and depletion of calcium abolishes interferon production. In addition, we have shown that interferon induction by concanavalin A, phytohemagglutinin, and staphylococcal enterotoxin A, but not by galactose oxidase is prevented by cleavage of N-acetylneuraminic acid residues. Thus, interferon induction in human lymphoid cell cultures by galactose oxidase, concanavalin A, phytohemagglutinin, staphylococcal enterotoxin A, and NaIO4 appears to reside in terminal oligosaccharides of the cell membrane. How this specific membrane event relates to the derepression of the interferon locus is being actively pursued.

Calcium↗