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Biomedical subjects

A Tagliabue

Publications and source records attributed to A Tagliabue.

At least 127 records · Page 7Linked to original sources
PubMed1982

Macrophage activation by interferon: dissociation between tumoricidal capacity and suppressive activity.

Resident peritoneal macrophages (M phi) from untreated mice and inflammatory M phi induced by a sterile irritant were able to exert significant suppressive activity on lymphocyte functions. M phi-mediated suppression was evident in lymphocyte proliferation and in a proliferation-independent lymphocyte response (i.e. lymphokine production). The lymphokine macrophage-activating factor (MAF), which enhances tumoricidal capacity of inflammatory but not of resident M phi in vitro, was ineffective in modulating suppressive activity of both resident and inflammatory M phi. In contrast, a significant effect on M phi-mediated suppression was observed upon treatment with IFN-beta. In fact, suppression of lymphoproliferation and of lymphokine production by either resident or inflammatory M phi was significantly decreased or abolished by IFN-beta. Like MAF, IFN-beta was able to increase M phi cytotoxicity against tumor cells. Such as effect, however, was evident in both resident and inflammatory M phi, thus confirming different M phi activation mechanisms for MAF and IFN-beta. These data indicate that IFN-beta acts mainly on mature M phi, which thus appear as the major M phi type involved in suppression. The contrasting effects of IFN-beta on M phi suppression and on M phi-mediated cytotoxicity strongly suggest a dissociation between the 2 induction mechanisms of suppression and cytotoxicity. The in vivo relevance of these two IFN activities was demonstrated by treating mice with the potent IFN inducer polyinosinic polycytidylic acid (poly(I).poly(C). M phi from poly(I).poly(C)-primed mice simultaneously showed enhanced tumoricidal activity and complete abolishment of suppressive capacity.

Animals↗
PubMed1982

IFN-beta-induced reduction of superoxide anion generation by macrophages.

Resident mouse peritoneal macrophages (M phi) produced significant amounts of superoxide anion (O2-) in response to phagocytic stimuli. When M phi were exposed in vitro for 20 hr to fibroblast interferon (IFN-beta), their capacity to release O2- was significantly reduced, such reduction being more evident with increasing IFN-beta concentrations. In contrast, O2- production by M phi exposed for 20 hr to the lymphokine macrophage activating factor (MAF) or treated with either MAF or IFN-beta for 4 hr was not significantly different from that of control cells. This pattern of activity closely followed that of M phi-mediated suppression of lymphocyte proliferation, which was dramatically reduced by 20 hr exposure of M phi to IFN-beta, but unchanged by treatment with MAF. No correlation was however found between superoxide anion generation and enhancement of tumoricidal capacity in IFN-beta-treated M phi. We thus concluded that O2- does not play a relevant role in IFN-beta-induced M phi cytolysis, whereas the reduction of O2- production could be of major importance in the decrease of M phi suppression induced by IFN-beta.

Animals↗
PubMed1981

Interferon-induced enhancement of macrophage-mediated tumor cytolysis and its difference from activation by lymphokines.

Mouse peritoneal macrophages expressed increased cytolytic activity against tumor cells upon in vitro exposure to partially purified L cell interferon (IFN-beta). In contrast, treatment with human IFN or with mock IFN preparations did not enhance macrophage tumoricidal capacity. Macrophage activation by IFN was optimal with long exposure times and high IFN concentrations. Treatment with polymyxin B sulfate did not affect IFN-induced macrophage cytotoxicity, thus excluding the possibility that bacterial lipopolysaccharide contaminants were responsible for macrophage activation. Conversely, treatment with a highly specific anti-IFN antiserum completely abolished IFN effect on macrophages, but had no effect on lymphokine-induced cytolysis. IFN and the lymphokine macrophage-activating factor (MAF) were compared for their ability to provide the sequence of activation signals to macrophages from the normal responder C3H/HeN mice and from C3H/HeJ mice, which are defective for several macrophage responses. Like MAF, IFN was incapable of inducing tumoricidal activity in C3H/HeJ macrophages. However, whereas MAF provided the first "priming" signal to macrophages of both strains, IFN acted as first signal only for C3H/HeN macrophages, being inactive for cells of the defective C3H/HeJ strain. Furthermore, IFN was not capable of providing the second "expression" signal to "primed" macrophages. These data suggest two different macrophage activation pathways for IFN and MAF.

Animals↗
PubMed1981

Natural killer activity of gut mucosal lymphoid cells in mice.

Intraepithelial lymphoid cells (IEL) obtained from the mucosa of mouse small intestine were tested for natural killer (NK) activity in a 20-h 51Cr-release assay against YAC-1 and RLfemale1 tumor cells. It was found that IEL possess a strong NK activity, higher than spleen cells, whereas lymphocytes from Peyer's patches (PPL) did not show any NK activity. The cytotoxic activity of IEL could be boosted by interferon (IFN-beta ) treatment, but no NK activity could be induced in PPL by in vitro IFN-beta treatment. The characteristics of the NK effector cells present in the mouse intestine strictly resemble those of NK cells in the spleen. In fact, intestinal NK activity is not affected by depletion of adherent cells and only partially reduced by anti-Thy-1.2 antibodies plus complement. Moreover, the age dependency of NK cytotoxicity is identical for IEL and spleen. Finally, NK-insensitive target cells are not lysed by IEL.

Aging↗
PubMed1981

Effects of in vivo treatments with cyclosporin-A on mouse cell-mediated immune responses.

The fungal metabolite Cyclosporin-A (CyA) was investigated for its activity on several cell-mediated immune responses. Oral administration of 70 mg kg-1 of CyA for 5 days to C3H/HeN mice completely abolished the in vivo antigen-dependent production of a lymphokine capable of increasing macrophage cytotoxicity against tumor cells. Moreover, spleen cells from CyA treated mice were significantly depressed in their ability to produce in vitro lymphokines in response to PHA, whereas only a slight depression was observed when ConA was employed to induce lymphokine production. In parallel to the depression of proliferation-independent immune response, spleen cells from CyA treated mice showed a strongly depressed proliferative response to PHA, marginal reduction being observed in the response to ConA. B-lymphocytes did not seem to be affected by in vivo treatment with CyA, judging from the proliferative responses to LPS. Macrophage responses also remained unaltered after CyA treatment. No depressions in natural or lymphokine-induced macrophage cytotoxicity and in monokine production were in fact observed in CyA treated mice. Finally, a short-lived depression of natural killer (NK) activity was observed after CyA administration. These results indicate that in vivo CyA treatment selectively depressed cell-mediated functions of lymphocytes of the T-cell lineage. The hypothesis that T-cell lineage. The hypothesis that T-helper lymphocytes are the preferential target of CyA immunodepression is discussed.

Animals↗
PubMed1981

Morphological characterization of a cell population responsible for natural killer activity.

Large granular lymphocytes (LGL) were observed in the peripheral blood, spleen, lung and, to a lesser extent, bone marrow and lymph nodes, but not in the thymus of C3H/HeN mice 8 weeks old. The organ distribution of natural-killer (NK) cytotoxicity closely followed that of LGL. Nude mice had higher LGL percentages and NK activity than normal mice. In addition, the age distribution of LGL from the peripheral blood followed that of NK activity. Employing discontinuous Percoll density gradients the percentage of LGL and the NK cytotoxicity of the low density fractions could be enriched in comparison with the original populations of lymphocytes from peripheral blood and spleen, but not from thymus. These results suggest that, as recently shown for humans and rats, in mice too LGL are associated with NK activity.

Animals↗
PubMed1980

Species-restricted effects of human and mouse lymphokines on macrophages.

Lymphokines produced by antigenic or mitogenic stimulation of human, guinea pig and mouse lymphocytes were tested for their effects on monocytes or macrophages of the same and heterologous species, to determine whether there is any species restriction in their reactivity. Supernatants from lymphocyte cultures were tested for migration inhibitory activity in an indirect agarose microdroplet assay and for their ability to augument cytolytic activity of macrophages or monocytes in a [3H]thymidine-release assay. Supernatants of human peripheral blood mononuclear cells, stimulated with phytohemagglutinin or purified protein derivative of tuberculin (PPD) were able to strongly inhibit the migration of human monocytes and guinea pig peritoneal exudate cells (PEC), but had no detectable effect on mouse PEC. The human supernatants could also significantly augment the cytolytic activity of human monocytes, but had no effect on cytotoxicity by mouse peritoneal macrophages. Conversely, supernatants of PPD-stimulated spleen cells from mice immune to bacillus Calmette-Guérin (BCG) strongly inhibited the migration of, and significantly augmented cytolysis by, mouse PEC, but had no detectable effects on human monocytes. Moreover, supernatants of concanavalin A-stimulated lymph node cells from guinea pigs inhibited the migration of guinea pig PEC and human monocytes, but had no effects on mouse PEC. The migration inhibitory effects of the human and mouse supernatants did not appear to be mediated by interferon (IF), since partially purified type-1 IF had no detectable effect. In addition, supernatants of human lymphocytes stimulated by Corynebacterium parvum strain 5888, that induced little or no IF, were able to inhibit the migration of, and augmented cytolysis by, human monocytes. These C.parvum supernatants also showed migration inhibitory activity on mouse PEC but did not induce cytolytic activity in these cells.

Animals↗
PubMed1979

Cytolytic activity of circulating human monocytes on transformed and untransformed human fibroblasts.

Monocytes from the peripheral blood of 10 normal adult human donors were tested for their cytolytic activity on untransformed or SV40-transformed, early passage, human fibroblasts. Two pairs of human fibroblast lines (2303 and SV40-2303, 2931 and SV40-2931) were used and lysis was assessed in terms of release of [3H]thymidine from prelabelled target cells over a 72-h incubation period. High levels of cytolytic activity were consistently observed on transformed fibroblasts at attacker to target cell (A:T) ratios ranging from 5:1 to 40:1. Low, but significant, lysis of untransformed cells was observed only with two donors at the highest (40:1) A:T ratio tested. With all donors, the cytolytic activity on transformed lines was significantly greater than on untransformed fibroblasts. Thus natural human monocyte-mediated cytotoxicity is preferentially expressed on transformed, as compared to untransformed, cells although sparing of the latter is not absolute.

Adult↗