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Biomedical subjects

B Mantovani

Publications and source records attributed to B Mantovani.

35 records · Page 2Linked to original sources
PubMed1987

Phagocytosis of in vitro-aged erythrocytes--a sharp distinction between activated and normal macrophages.

Phagocytosis experiments performed in vitro in the absence of serum with mouse peritoneal macrophages have shown that normal macrophages can bind to in vitro-aged sheep red blood cells without antibody or complement, but only activated macrophages are able to ingest these erythrocytes. This sharp qualitative functional difference may be an index for the characterization of the activated state of macrophages.

Animals↗
PubMed1985

[Intravenous administration of lidocaine and amiodarone in patients with acute myocardial infarction].

Lidocaine (L) in still considered the drug of choice in the treatment of life threatening ventricular arrhythmias in the setting of acute myocardial infarction (A.M.I.): this is mainly due to its proved efficacy and high therapeutic index. Since however L has well defined electrophysiologic properties (class 1 B) and does not seem to be effective in all of these patients we compared its antiarrhythmic efficacy with the one of amiodarone (A), an antiarrhythmic agent provided of electrophysiologic properties quite different from L (class 4) and usually well tolerated. Twenty-five consecutive patients with A.M.I. without haemodynamic consequences, were randomly assigned to L (bolus of 1 mg/kg followed by an infusion of 10 mg/min for 20 minutes and thereafter of 1,5 mg/min) or A (bolus of 5 mg/kg and an eventual repeat dose of 150 mg followed by an infusion of 1,8 g/24 h) The baseline arrhythmia was classified as Lown class 2 ore more in all the patients. The ventricular arrhythmias were completely relieved in 47% of the patients assigned to L and in 60% of those treated with A (p = N.S.); a minor efficacy was found in 40% of the patients of both groups; in two cases ventricular fibrillation occurred after the acute infusion of L. The antiarrhythmic effectiveness kept fit with both drugs over a 24 hours period. A prolongation of QTc interval was found to occur both after the bolus and 24 hours of treatment with A. In addition A provoked a slight decrease of systolic blood pressure. No important side effects were observed with both drugs regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1984

Lysosomal enzyme release from polymorphonuclear leukocytes induced by immune complexes of IgM and of IgG.

Lysosomal enzyme release by rabbit polymorphonuclear leukocytes induced by immune complexes of IgM or IgG antibodies and ovalbumin was studied by in vitro experiments. It was shown that IgM immune complexes in the form of precipitates were able to stimulate the release of the lysosomal enzymes beta-glucuronidase and alkaline and acid phosphatases, in contrast to heat-aggregated IgM, which had only a small effect. This stimulation was dependent on the presence of Ca2+ in the extracellular medium; Mg2+ showed a slight effect as a substitute for Ca2+. IgG precipitated immune complexes prepared from different regions of the precipitation curve were tested. It was shown that immune precipitates from the equivalence region were the most effective; those at antibody excess have a smaller but comparable capacity, whereas the precipitated immune complexes at antigen excess were the least effective. Soluble immune complexes of IgG with an excess of antigen concentration in the range of 2.5 to 5 times that of equivalence were also able to stimulate the enzyme release, but that capacity decreased rapidly with the increase in antigen concentration. The enzyme release induced by IgM immune complexes was not inhibited by competition with free immunoglobulin in the medium, either IgM or IgG in approximate physiologic concentrations; contrarily, with IgG immune complexes, free monomeric IgG (but not IgM) can completely block the process. The possible implications of these findings in the immune complex diseases are discussed.

Animals↗
PubMed1982

Quantitative histochemical studies of the effect of levamisole on splenic T-cells in thymectomized Bufo bufo larvae.

The ability of levamisole (LVS) to correct the effect of thymectomy on splenic T-cell population in Bufo bufo larvae was tested. Using the nonspecific acid alpha-naphthyl acetate esterase (ANAE) technique, the T-lymphocytes displayed a characteristic reddish brown spot (T-pattern). The total number of white cells per spleen and the number of T-pattern cells per 100 splenic white cells were determined. In addition, differential counts of the T-patterns were made on the basis of the size of their spots. Thymectomized larvae in comparison to sham-operated larvae possessed a lower total number of splenic white cells with a similar proportion of T-pattern cells, but a lower proportion of cells with a large T-pattern. After seven days of LVS treatment, the thymectomized larvae showed an increased total number of splenic white cells and an increased proportion of cells with a large T-pattern, both data falling within normal limits. The effect of LVS appeared marked in thymectomized larvae, but was slight or absent in sham-operated larvae. Differential counts of the large T-pattern cells, based on the size of ANAE reaction product, showed the capacity of LVS to stimulate T-cell maturation. It was concluded that LVS induced proliferation and differentiation of splenic T-cells and that the different sizes of T-pattern reaction represent different maturational stages of T-cells.

Animals↗
PubMed1982

Chemical modification of IgG tryptophan residues: effect on competition with immune complexes for macrophage receptors.

1. The effect of benzylation of tryptophan residues of immunoglobulin G (IgG) on the interaction with macrophage receptors was studied by measuring the competition between free IgG and immune complexes (sheep red cells covered with IgG antibodies). 2. The modification of approximately three tryptophan side chains greatly decreased the capacity of IgG for binding to the phagocytic cell. Under conditions in which normal IgG inhibited the binding of immune complexes to macrophages by 49 +/- 5% and the urea-treated IgG control inhibited it by 40 +/- 11%, IgG modified by 2-hydroxy-5-nitrobenzyl bromide in the presence of urea inhibited the binding by 7.5 +/- 5%. 3. These results indicate that tryptophan residues are located at or near the site of IgG that binds to the macrophage receptor and that they are important for the interaction.

2-Hydroxy-5-nitrobenzyl Bromide↗
PubMed1981

Phagocytosis of immune complexes mediated by IgM and C3 receptors by macrophages from mice treated with glycogen.

Phagocytosis mediated by IgM and C3 receptors was studied by in vitro experiments with peritoneal macrophages from mice treated with repeated i.p. injections of glycogen. The immune complexes were sheep red cells sensitized with mouse IgM antibody or antibody and complement. Macrophages from the inflammatory exudate induced by glycogen were able to phagocytize immune complexes of red cells and IgM antibodies in contrast to normal macrophages, which can only bind to these complexes. Evidence was also found for phagocytosis mediated by interaction with C3 receptors in the macrophages from the glycogen-treated animals. The implications of these findings in the mechanism of phagocytosis and the possible relevance of the observed changes in the function of macrophage receptors for the afferent and efferent branches of immune response are discussed.

Animals↗
PubMed1978

Cooperative cross-linking between two sets of membrane receptors: a model for B and T lymphocyte collaboration in immune response.

A molecular mechanism for B and T lymphocyte collaboration is proposed. Two sets of polivalent receptors, each one on a cell type, would interact with different epitopes of the antigen, resulting in a cross-linking of the receptors as the initial step in B lymphocyte activation. The mechanism can explain many known featrues of humoral immune response and accords with experimental findings on the blast transformation of B lymphocytes.

Antibody Formation↗
PubMed1975

Different roles of IgG and complement receptors in phagocytosis by polymorphonuclear leukocytes.

The functions of IgG and complement receptors in phagocytosis of immune complexes by mouse polymorphonuclear leukocytes were examined by in vitro experiments. The immune complexes were sheep red cells (E) sensitized with IgG antibody (EA) or with antibody and complement (EAC). Inhibition experiments with Fab fragments of rabbit IgG antibody anti-mouse IgG have shown that the complement receptor is primarily involved in the attachment phase, whereas participation of the IgG receptor is necessary for inducing the mechanism of phagocytosis. The possible relevance of these findings for the in vivo mechanism of defense infection, and for the control of antibody synthesis is discussed.

Animals↗
PubMed1972

Phagocytosis of immune complexes by macrophages. Different roles of the macrophage receptor sites for complement (C3) and for immunoglobulin (IgG).

Sheep red cells (E) sensitized with IgG antibody (EA) or with antibody and complement (EAC) interact in vitro with mouse peritoneal macrophage monolayers. The role of IgG and of C3 in the attachment and ingestion of the erythrocytes was examined by means of quantitative technique utilizing (51)Cr-labeled E. Controlled osmotic lysis permitted the separate measurement of the radioactivity associated with bound or with ingested E. IgG-(125)I was used to estimate the number of IgG molecules bound per E as a function of the IgG concentration. Control experiments showed that iodination did not influence the extent of binding of IgG to E and that the binding of IgG prepared from immune serum could be essentially ascribed to its anti-E antibody content. Only between 10(3) and 10(4) rabbit anti-E IgG molecules per erythrocyte were needed for detectable attachment and ingestion of EA (a maximum number of 6 x 10(5) IgG antibody molecules could be accomodated on one erythrocyte). Evidence was obtained that C3 is primarily involved in particle attachment, whereas only IgG is able to markedly promote the ingestion of particles attached to macrophages: (a) Addition of complement to the EA substantially increased the binding to the macrophages, whereas ingestion was increased to a smaller extent. Both binding and ingestion of EAC were markedly inhibited by papain fragments of IgG obtained from a rabbit antiserum to mouse C3. (b) Low doses (2 microg/ml) of papain fragments of IgG from a rabbit antiserum to mouse IgG markedly reduced the ingestion of EAC, whereas attachment of EAC to macrophages was inhibited to a much smaller degree. The possible relevance of these findings for the in vivo fate of particulate immune complexes as they interact with macrophages is discussed. It is suggested that in the primary immune response, when the complexes are predominantly in the form of EA (IgM) or EA (IgM) C3, they would tend to remain on the surface of the macrophages and thus be in a position to stimulate immunocompetent cells. In the secondary response, when EA (IgG) or EA (IgG) C3 predominate, the complexes would tend to be more rapidly interiorized and degraded by the mononuclear phagocytes,

Animals↗
PubMedDate not supplied

Retinoids and cancer: antitumoral effects of ATRA, 9-cis RA and the new retinoid IIF on the HL-60 leukemic cell line.

OBJECTIVE: To compare the antitumoral effects of all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA) with those of 5-OH,11-O-hydrophenanthrene (IIF), a new derivative of retinoic acid. MATERIALS AND METHODS: The effect of retinoids was tested on cell line HL-60. Cell differentiation and apoptosis were evaluated by morphological and biochemical analysis as BCL-2 protein and by DNA fragmentation assay. The ability to activate retinoic acid receptors (RAR) and/or retinoid X receptors (RXR) and to modulate gene expression was determined by transactivation assay. RESULTS: With cell line HL-60, the antiproliferative effect of IIF was stronger than that of ATRA and 9-cis RA. Following retinoid treatment, cells appeared to differentiate and apoptotic cells were observed. The appearance of DNA laddering and a decrease in the amount of BCL-2 protein confirmed apoptosis. IIF transcriptionally activated RXR-gamma more than RAR-alpha. CONCLUSION: The findings indicate that IIF transcriptionally activates RXR-gamma preferentially, induces apoptosis and has a more antiproliferative activity than ATRA and 9-cis RA on cell line HL-60.

Animals↗
PubMedDate not supplied

Retinoids and cancer: antitumor effect of ATRA and of a new derivative of retinoic acid, IIF, on colon carcinoma cell lines CaCo-2 and HT-29.

Vitamin A and its metabolic forms, like all-trans retinoic acid (ATRA), are used with promising results in the treatment of many tumors. Two major problems in the clinical use of retinoids are that the doses needed for successful treatment are often toxic, leading to "hypervitaminosis A syndrome" and that patients often develop drug resistance. In order to find compounds that can overcome these problems, many new derivatives of retinoids have been synthesized and tested. Here we present a study on the effect of a new derivative of retinoic acid, IIF (pat. WIPO W0 00/17143), on growth and differentiation of two colon carcinomna cell lines, CaCo-2 and HT-29, with different degrees of tumorigenicity, the second one being more undifferentiated. The effect of IIF was compared with that of ATRA, whose antitumoral action on colon cancer cells and other tumoral cells is widely described in the literature. Besides exerting a strong antiproliferative effect, even higher than that of ATRA, IIF induced cellular differentiation, as demonstrated by the appearance of morphological (domes and microvilli formation) and biochemical (alkaline phosphatase induction) markers. Therefore, these findings indicate the new retinoid IIF as a possible candidate in the treatment of colon cancer.

Antineoplastic Agents↗