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Biomedical subjects

A Tagliabue

Publications and source records attributed to A Tagliabue.

At least 109 records · Page 6Linked to original sources
PubMed1985

Regulation of arachidonic acid metabolism in macrophages by immune and nonimmune interferons.

Mouse resident peritoneal M phi release AAA and metabolize it into cyclooxygenase- and lipoxygenase-derived eicosanoids, when triggered in vitro with different stimuli. Pretreatment of M phi with nonimmune IFN-alpha and IFN-beta dramatically decreased AA liberation from M phi phospholipids and eicosanoid formation after stimulation of M phi with Zy, A23187, or PMA. M phi exposed to immune IFN-gamma also showed a substantial impairment of both AA liberation and eicosanoid production upon exposure to Zy. However, AA and eicosanoid release was increased by IFN-gamma, rather than depressed, in PMA-triggered M phi. In addition, IFN-gamma showed differential effects on M phi stimulated with A23187. In fact, it inhibited AA release as well as formation of lipoxygenase-derived LTC4, but it highly increased the release of the cyclooxygenase products PGE2 and 6-keto PGF1 alpha. The ability of IFN-gamma to differentially modulate AA metabolism of M phi, depending on the nature of the triggering agent, sets forth the high specificity of the regulatory capacity of this molecule. This is at variance with the down regulation of AA metabolism that is generally observed with nonimmune IFN.

Animals↗
PubMed1985

In vitro generated mast cells express natural cytotoxicity against tumour cells.

Bone marrow cells from mice were cultured in vitro in the presence of interleukin-3 (IL-3). After 2 weeks, the majority of the cells differentiated towards mast cells as judged by morphological and biochemical criteria. When populations of 99% IL-3-dependent mast cells (IL-3 MC) were tested for their anti-tumour activity in vitro, it was found that they can express natural cytotoxicity (NC) but not other natural reactivities. Moreover, the effector cells were not positive for Thy 1, Lyt 1 and Lyt 2 markers. The capability of mast cells to express NC activity seems to be related to their in vitro differentiation, since mast cell deficient W/Wv mice had normal NC activity. Thus, IL-3 MC must be added to the variety of cells capable of expressing natural anti-tumour reactivities in vitro.

Animals↗
PubMed1985

Natural anti-bacterial activity against Salmonella typhi by human T4+ lymphocytes armed with IgA antibodies.

Peripheral blood mononuclear cells from normal volunteers possess natural anti-bacterial (NA) activity against S. typhi that can be measured in a 2-hr in vitro assay. Employing fractionation on nylon wool columns, Percoll gradients, plastic adherence, and E rosetting, the effector cell of NA activity appeared to be a lymphocyte of the T lineage rather than a macrophage, a B lymphocyte, or a large granular cell. Moreover, complement-dependent killing with monoclonal antibodies such as OKM1, OKB7, OKT8, 5.9 and the anti-natural killer cells AB8.28 did not reduce NA activity. On the contrary, this was completely inhibited when OKT3, OKT11, or OKT4 antibodies and complement were used to pretreat the effector lymphocytes. Indeed, T4+ cells sorted with a FACS displayed an extremely high NA activity against S. typhi. By pretreatment of peripheral lymphocytes with F(ab')2 fragments against human IgA, the NA activity was blocked. It is therefore suggested that NA activity by human cells might be a mechanism of defense against infections, acting as antibody-dependent cellular cytotoxicity expressed by T4+ lymphocytes coated with preexisting anti-Salmonella IgA antibodies.

Antibodies, Bacterial↗
PubMed1984

Macrophage antitumor activity: impaired responsiveness to interferon-gamma of macrophages from genetically defective mice.

Macrophages (M phi) from the genetically defective mouse strains C3H/HeJ, A/J and P/J were unable to develop high levels of antitumor activities when stimulated either with immune recombinant interferon gamma (IFN-gamma) or with nonimmune IFN-alpha and IFN-beta, as compared to M phi or normal C3H/HeN mice. IFN-gamma appeared to be an exceptionally good activator of C3H/HeN M phi, as it could induce tumoricidal capacities 3000 times more efficiently than nonimmune IFN. The high efficiency of IFN-gamma as M phi activator was indeed confirmed on defective M phi. In fact, at high doses IFN-gamma could also induce significant levels of both cytolytic and cytostatic activity in M phi of A/J and P/J mice, although it could not increase cytotoxic activities of C3H/HeJ M phi.

Animals↗
PubMed1984

Identification and synthesis of an antigenic determinant common to human chorionic somatomammotropin and human growth hormone.

Human chorionic somatomammotropin (hCS) and human growth hormone (hGH), despite their different biological activities, show a remarkable degree of homology in their primary structure, which explains their immunological cross-reactivity. On the basis of the hydrophilicity profiles, we predicted that the sequence 165-174 would correspond to an antigenic determinant common to both hormones. The sequence 165-174 was synthesized in the solid phase and the ability to bind antibodies to hCS was tested by a radioimmunoassay at each step of the synthesis, without detaching the peptide from the resin. We found that the immunological sequence able to bind antibodies to hCS is that corresponding to 167-174. In similar experiments, we showed that the sequence 166-174 is able to bind antibodies to hGH. In the plaque-forming cell test using the synthetic fragment 166-174 bound to sheep red blood cells, we also observed that the ratio between the number of cells forming antibodies to hCS and to the 166-174 peptide was always between 0.45 and 0.73, thus suggesting that the 166-174 peptide represents a major determinant of hCS.

Amino Acid Sequence↗
PubMed1984

Macrophage antitumor activity in vitro. Comparative analysis of cytolytic, cytostatic, and cytotoxic activities of mouse macrophages and human monocytes.

Mouse peritoneal M phi and human blood monocytes were assayed for their antitumor activity in vitro with a cytolysis, a cytostasis and a cytotoxicity test performed in parallel. Both natural and stimulus-induced M phi antitumor capacities were assessed. Results indicate that natural cytolytic activity of unstimulated M phi is generally unable to restrict final tumor cell growth, since it is not coupled with cytostatic capacity. In contrast, exposure of M phi in vitro to either MAF or IFN-beta, besides augmenting M phi cytolytic capacity, induced a very significant cytostatic activity and thus efficiently restricted the survival of tumor cells.

Animals↗
PubMed1984

Interferon inhibits prostaglandin biosynthesis in macrophages: effects on arachidonic acid metabolism.

Mouse resident peritoneal M phi produced considerable amounts of PGE when triggered in vitro with soluble or particulate stimuli. Preexposure of M phi to IFN-beta dramatically decreased PGE production. This effect depended on the dose of IFN-beta used and was abolished by anti-IFN-beta globulin. In addition to PGE, other AA metabolites of the cyclooxygenase pathway, namely TXB2 and 6-keto PGF1 alpha, were decreased in IFN-beta-treated M phi. However, IFN-beta did not have any effect on cyclooxygenase activity of M phi, indicating that an earlier step of PG biosynthesis was likely to be the target of its inhibitory action. Indeed, the release of radioactive compounds from M phi prelabeled with [14C]AA was strongly impaired by IFN-beta, suggesting that IFN-beta would decrease PG production in M phi by blocking phospholipase activation. The possibility that the IFN-beta effect on phospholipase could be mediated through the increase of the intracellular levels of cAMP is suggested.

Animals↗
PubMed1984

Indirect leukocyte migration inhibition in breast cancer and benign breast disease patients by mouse mammary tumor virus grown in feline kidney cells.

Indirect migration inhibition assays were performed with normal and mammary tumor-bearing C3H/HeN mice and patients with breast disease to assess cellular immunity against three different mouse mammary tumor virus (MTV) preparations grown in feline kidney cell cultures and against a mouse-derived MTV preparation. MTV obtained after passage through feline kidney cells and the mouse-derived MTV were capable of eliciting macrophage migration inhibitory factor production by mouse spleen cells obtained from normal or mammary tumor-bearing C3H/HeN mice, thus demonstrating a similar degree of antigenicity of these preparations. In experiments with human breast cancer patients' leukocytes, leukocyte inhibitory factor (LIF) was produced by 32-50% of these patients in response to the mouse-derived MTV or to three different MTV preparations obtained after passage through feline kidney cells. A significant proportion (31-54%) of benign breast disease patients also reacted with both the mouse-derived and feline-derived MTV preparations. Patients with both malignant and benign breast disease, however, had a significantly different (P less than .05) pattern of reactivity to mouse- and feline-derived MTV preparations from that observed with normal donors. Finally, some LIF activity was also observed (but not statistically significant with the use of nonparametric analysis methods) when feline leukemia virus was used as antigen with these patients. The data suggest that both breast cancer and benign breast disease patients were reactive against antigens largely specific for MTV in the feline cells and, presumably, were not reactive against feline cellular components, although the second possibility cannot be completely ruled out.

Animals↗
PubMed1984

Interferon-gamma reduces macrophage-suppressive activity by inhibiting prostaglandin E2 release and inducing interleukin 1 production.

Normal peritoneal M phi of C3H/HeN mice were able to suppress lymphocyte proliferation in a dose-dependent fashion when added to Con A-pulsed spleen cell cultures. However, M phi-suppressive activity could be partially or completely reduced by in vitro pre-exposure to nonimmune IFN-alpha or immune recombinant IFN-gamma. For both IFN-alpha and IFN-gamma, reduction of M phi suppression was marginal at 10(1) U/ml and became highly significant at 10(2) to 10(3)/ml. The ability of IFN-alpha and IFN-gamma to modulate M phi suppression appears to be related to distinct mechanisms. In fact, impairment of M phi suppression by IFN-alpha occurred in parallel to the decrease of M phi capacity to produce PGE2 and the oxygen intermediate O2-, two molecules responsible for M phi-suppressive activity. In contrast, M phi exposed to IFN-gamma showed only impairment of PGE2 production, whereas O2- release was not significantly affected. Furthermore, at variance with IFN-alpha, IFN-gamma directly stimulated M phi to synthesize and release IL 1, a monokine known to promote lymphocyte proliferation.

Animals↗
PubMed1984

IgA-dependent cell-mediated activity against enteropathogenic bacteria: distribution, specificity, and characterization of the effector cells.

Antibody-dependent cellular cytotoxicity (ADCC) against murine enteropathogenic bacteria such as Salmonella typhimurium and Salmonella tel aviv or Shigella X16 was assessed by using IgG, IgA, and secretory IgA (sIgA) in a 2-hr in vitro assay where peripheral and intestinal lymphocytes were used as effector cells. It was found that IgG could arm splenocytes (SpL) better than IgA. However, IgG did not arm lymphocytes from Peyer's patches (PPL) or from mesenteric lymph nodes (MnL), whereas IgA of plasmacytoma origin against S. tel aviv and purified intestinal sIgA against Shigella X16 induced specific antibacterial ADCC with both SpL and PPL. When sIgA were tested with intestinal lymphocytes from the epithelium and the lamina propria, i.e., cells from the gut mucosa which first interact with enteric bacteria, it was found that both these lymphoid populations were able to express sIgA-dependent ADCC against Shigella X16. In parallel tests, cells from thymus and popliteal lymph nodes failed to express ADCC. Blocking studies with purified IgG and IgA of goat, rabbit, and mouse origin demonstrated that the Fc-alpha and Fc-gamma receptors were specifically involved in IgA- or IgG-dependent antibacterial ADCC. At least two effector populations, a macrophage and a Thy-1.2- lymphocyte, were observed to exert IgA-ADCC at the splenic level, whereas only lymphoid cells expressed this activity at the GALT level. Together, these results describe a new activity of IgA against enteropathogenic bacteria.

Animals↗
PubMed1984

Genetic control of in vitro natural cell-mediated activity against Salmonella typhimurium by intestinal and splenic lymphoid cells in mice.

In vitro natural anti-bacterial activity against Salmonella typhimurium by lymphocytes from Peyer's patches and spleens was assessed in several mouse strains. C3H/HeN and CBA/J mice, which are resistant to S. typhimurium infections, showed a natural anti-bacterial activity significantly higher than BALB/c, C57BL/10, C57BL/6 and C3H/HeJ mice, i.e. strains susceptible to the in vivo bacterial infection. In these susceptible strains and also in A/J mice, a significantly higher natural activity was observed in females compared to males. The sex control of natural anti-bacterial activity was further stressed by the fact that orchidectomy could induce a strong activity in low responder C57BL/10 male mice. With the exception of Beige mice, a low natural killer (NK) strain also with no natural activity against S. typhimurium in both sexes, the genetic distribution of natural anti-bacterial activity was extremely different from that of the NK activity. Thus, these results further stress the difference between natural anti-bacterial activity and NK cytotoxicity. Furthermore, our data establish a possible link, although with some exceptions, between in vivo susceptibility to S. typhimurium infections and in vitro natural activity against these bacteria.

Animals↗
PubMed1984

Modulation of macrophage suppressive activity and prostaglandin release by lymphokines and interferon: comparison of alveolar, pleural and peritoneal macrophages.

In order to better characterize the mechanisms which regulate the immune response at the pulmonary level, the effects of beta-interferon (IFN-beta) and lymphokines (LK) on prostaglandin E (PGE) release and the suppressive capacity of mouse resident alveolar (AM phi) and pleural macrophages (PlM phi) were investigated in comparison with peritoneal macrophages (PM phi). After in vitro exposure to IFN-beta, PlM phi and PM phi showed a significant decrease of suppressive capacity and PGE release, whereas LK treatment did not affect such activities. In contrast, pre-treatment of AM phi with LK caused a strong impairment of their suppressive capacity. This effect was optimal after an incubation time of 20 h, was evident also at very low doses of LK and was not paralleled by any change of PGE release. Again in contrast with PlM phi and PM phi, suppressive capacity of AM phi was decreased only by very high doses of IFN-beta, whereas lower doses caused either an increase or no change of this activity. Furthermore, PGE release by AM phi was markedly increased after treatment with IFN-beta. Thus, suppressive capacity of AM phi appears to be controlled by different mechanisms from those of PlM phi and PM phi. In addition, a dissociation is evident between suppressive capacity and PGE release by AM phi.

Animals↗
PubMed1983

Dissociation between macrophage tumoricidal capacity and suppressive activity: analysis with macrophage-defective mouse strains.

Macrophages (M phi diameter) from three mouse strains with genetically distinct M phi diameter deficits (C3H/HeJ, A/J, and P/J) were unable to develop high cytolytic and cytotoxic activity against tumor cells in vitro when exposed to agents (MAF and IFN-beta) that strongly increased the tumoricidal capacity of M phi diameter from nondefective C3H/HeN mice. Nevertheless, the tumoricidal deficits of M phi diameter from the defective strains did not affect their suppressive capacity on Con A-induced lymphoproliferation, nor their ability to react to IFN-beta by decreasing suppressive activity. In fact, natural suppressive activity and IFN-beta-induced changes in the suppression of M phi diameter from C3H/HeJ, A/J, and P/J mice were highly comparable to those of C3H/HeN M phi diameter, thus stressing the dissociation between the mechanisms governing M phi diameter suppression and M phi diameter tumoricidal activity. Analysis of the modulation by MAF and IFN-beta of M phi diameter ability to release the oxygen metabolites O2- and H2O2, molecules possibly involved in the effector mechanism of both M phi diameter cytotoxicity and suppression, revealed a close correlation with the patterns of suppressive activity in both nondefective and defective strains. In contrast, no correlation between the production of oxygen-reactive species and M phi diameter tumoricidal activity was observed. The ability of MAF- and IFN-beta-treated M phi diameter to produce PGE, a molecule of major importance in M phi diameter-mediated suppression and possibly involved also in the regulation of M phi diameter tumoricidal activity, again paralleled M phi diameter suppressive capacity. Thus, the mechanisms controlling M phi diameter antitumor activity appeared to be clearly distinct from those involved in M phi diameter suppression.

Animals↗
PubMed1983

Natural and antibody-dependent cell-mediated activity against Salmonella typhimurium by peripheral and intestinal lymphoid cells in mice.

Cell-mediated immune responses were assessed employing a 2-hr in vitro cytotoxicity assay against S. typhimurium. It was observed that lymphocytes from GALT as well as from peripheral lymphoid organs possessed natural antibacterial activity, whereas macrophages were devoid of this spontaneous activity. The distribution of this newly described natural activity was PPL greater than MnL greater than IEL = SpL = PBL greater than PoL; this did not correlate with the organ distribution of NK activity against YAC-1 tumor cells, which was PBL greater than SpL = IEL greater than MnL = PoL = PPL. Moreover, the phenotype of the splenic effector cell of the natural activity against S. typhimurium showed some differences from that of NK activity. In fact, both these cells were asialo GM1+, Fc-receptor+, nonadherent, and nonphagocytic, but the former was Thy-1.2- and the latter Thy-1.2+. The effector cell of the natural antibacterial activity in the Peyer's patches had the same phenotype as the splenic one. It was then observed that the antibacterial activity could be augmented by the addition of immune antibodies against S. typhimurium. This was particularly evident employing IEL, SpL, and PBL as effector cells, whereas PPL and MnL did not show any antibody-dependent antibacterial activity. Furthermore, these last two populations could not mediate ADCC against CRBC. Employing selective methods to deplete cell populations, we observed that, at least at the splenic level, there is also a cell that differs in its phenotypic characteristics from that mediating natural antibacterial activity but that plays a role in the antibody-dependent reactions. In conclusion, these results suggest that natural and antibody-dependent antibacterial mechanisms might be important in defense against S. typhimurium, particularly at the gastrointestinal level, where many bacterial infections first take place and begin to interact with the host immune system.

Animals↗
PubMed1983

Interferon decreases production of hydrogen peroxide by macrophages: correlation with reduction of suppressive capacity and of anti-microbial activity.

Mouse peritoneal macrophages (M phi) expressed enhanced tumoricidal activity upon in vitro stimulation either with the lymphokine M phi-activating factor (MAF) or with fibroblast interferon (IFN-beta). In contrast, M phi suppressive activity on lymphoproliferation was not affected by MAF pretreatment, but was drastically reduced or abolished by IFN-beta. Catalase, the enzyme involved in the destruction of hydrogen peroxide (H2O2), did significantly decrease M phi suppressive capacity but had no effect on M phi tumoricidal activity. Analysis of the phagocytosis-dependent H2O2 production by IFN-beta-treated M phi demonstrated a strong impairment of the oxygen metabolite release, which strictly paralleled the decreased M phi suppressive capacity. On the other hand, MAF did not modify H2O2 release by M phi. Studies on M phi antibacterial activity against Salmonella typhimurium, a function thought to depend upon H2O2 production, showed that exposure of M phi to IFN-beta significantly impaired their bactericidal and bacteriostatic capacity, again in close correlation with the decrease in H2O2 production. Thus, IFN-beta appears as modulating both suppressive and antibacterial capacities of M phi through reduction of their oxygen metabolism, whereas regulation of M phi anti-tumour activity is possibly controlled by different mechanisms.

Animals↗
PubMed1982

Meningeal leukemia following lymphoid blast crisis in chronic myeloid leukemia: therapeutic implications.

Five of 40 patients with chronic myeloid leukemia (CML) had lymphoid blast crisis and 4 of them achieved complete remission of metamorphosis with vincristine and prednisone. While in hematologic remission, two of these subjects developed meningeal leukemia. Clinical and biologic data indicated that the course of the disease after lymphoid blast crisis was very similar to that of acute lymphoblastic leukemia (ALL). It is suggested that patients with CML who develop lymphoid blast crisis should be treated with an intensive therapeutic protocol including early prevention of meningeal leukemia.

Adolescent↗
PubMed1982

Characteristics of natural killer cells in the murine intestinal epithelium and lamina propria.

Highly purified populations of lymphocytes were obtained from the murine intestinal mucosa using EDTA-collagenase isolation procedures in combination with discontinuous density centrifugation. Intraepithelial lymphocytes (IEL) were separated from lamina propria lymphocytes (LPL) and, within these two populations, fractions enriched or depleted in gut granular lymphocytes (gGL) were obtained. Using these cells in cytotoxic assays, it was shown that both IEL and LPL possess natural killer (NK) activity, and this was associated with gGL. The major effector cells of gut NK activity appeared to be Thy-1.2+, Lyt-1.1-, and Lyt-2.1-. The susceptibility of gut NK cells to anti-Thy-1.2 plus complement (C) was significantly higher than that of splenic NK cells. In contrast, anti-asialo GM1 and anti-NK-1.2 plus C only slightly affected the gut NK activity. Thus, the phenotype of the gut NK cells appears to be different from the splenic one and provides further evidence for NK heterogeneity and establishes the compartmentalization of one NK subpopulation. Beige mice, deficient in splenic NK activity, also had very low gut NK activity. W/Wv mice, which lack mast cell precursors, had normal numbers of gGL and diminished, but still present, gut and splenic NK activity. This deficiency did not segregate with the genes responsible for the basic hemopoietic stem cell defect, and these results argue against a close ontogenetic relationship between IEL, gGL, and intestinal mucosal mast cells. The relevance of these observations to the cell lineage of the effector cell of gut NK activity is discussed.

Animals↗