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A Toraño

Publications and source records attributed to A Toraño.

10 recordsLinked to original sources

Leishmania immune adherence reaction in vertebrates.

In normal human blood, C3-opsonized Leishmania promastigotes immune adhere to erythrocytes, a mechanism believed to enhance their clearance from blood and phagocytosis. Given the potential importance of this reaction in host defence against infection, the promastigote-erythrocyte interaction was studied in blood of individuals from one avian and 12 mammalian genera; [111In]-labelled promastigotes were found to bind only to primate erythrocytes. Nevertheless, previous experiments coincubating platelets isolated from nonprimate mammals with C3-opsonized promastigotes led to promastigote-platelet adherence. To ascertain whether this is a natural mechanism in nonprimate Leishmania infection, normal blood from members of Leishmania animal models of interest, dog, guinea-pig, hamster, mouse and rabbit, was infected ex vivo with promastigotes. Within 1 min of blood contact, the promastigote surface was loaded with platelets, rapidly evolving into large aggregates. These results confirm the physiological nature of the reaction and demonstrate that promastigote-erythrocyte and promastigote-platelet binding are the first parasite-host cell encounters after Leishmania invasion of primates and nonprimate mammals, respectively. Leishmania immune adherence shares the characteristics of the nonanticipatory immune systems, and we consider it should be viewed as an innate vertebrate host effector mechanism.

Animals↗

Bile acid secretion during rat liver carcinogenesis.

Retro-differentiation of liver parenchyma during neoplastic processes is characterized by the expression of tumor antigens, such as alpha-fetoprotein and the placental isoenzyme of glutathione-S-transferase (GST-P). To investigate whether this may also affect a typical liver function such as bile acid secretion was the aim of this work. Rat hepatocarcinogenesis was induced by diethylnitrosamine (i.p., 200 mg/Kg body weight at day 0) and promoted by two-thirds partial hepatectomy (at day 21) plus 2-acetamidofluorene administration (50 mg/Kg body weight, subcutaneously, twice a week from day 14 to day 35). In order to carry out planimetric measurements of neoplastic tissue after immunohistochemical staining, a novel monoclonal antibody (MAb 14.1.3) against GST-P with no cross-reactivity against the major liver isoform of GST (GST-H) was raised. Analysis of total biliary bile acid output using the 3alpha-hydroxysteroid dehydrogenase method indicated that a significant reduction (-26%) occurred during the formation of GST-P-positive foci (12 wk). This was restored to normal values during adenoma formation (16-20 wk), but decreased again during carcinoma transformation (32 wk). These changes were not parallel to that observed in bile flow, which was progressively but slightly decreased throughout the whole period under study. HPLC analysis of bile samples collected for 1 h at different time points during hepatocarcinogenesis revealed that in contrast to what happens during cholestatic disease, a continuous and progressive increase in the cholic acid-to-chenodeoxycholic acid ratio (from 4.4+/-0.5 in control animals to 15.1+/-1.9 in rats with hepatocellular carcinoma) occurs. A significant and transient increase at 16 wk (+120%) in the proportion of bile acids amidated with glycine as compared to those conjugated with taurine was also observed. These results indicate that the mechanisms accounting for the secretion of major bile acids are modified differently at various steps of rat liver tumor development.

2-Acetylaminofluorene↗

Immune adherence-mediated opsonophagocytosis: the mechanism of Leishmania infection.

To mimic the sandfly pool feeding process and characterize the cellular and biochemical events that occur during the early stages of promastigote-host interaction, we developed an ex vivo model of human blood infection with Leishmania promastigotes. Within 30 s of blood contact, Leishmania promastigotes bind natural anti-Leishmania antibodies, which then activate the classical complement pathway and opsonization by the third component of complement. The opsonized promastigotes undergo an immune adherence reaction and bind quantitatively to erythrocyte CR1 receptors; opsonized Leishmania amastigotes also bind to erythrocytes. Progression of infection implies promastigote transfer from erythrocytes to acceptor blood leukocytes. After 10 min of ex vivo infection, 25% of all leukocytes contain intracellular parasites, indicating that blood cells are the early targets for the invading promastigotes. We propose that adaptation to the immune adherence mechanism aids Leishmania survival, promoting rapid promastigote phagocytosis by leukocytes. This facilitates host colonization and may represent the parasite's earliest survival strategy. In light of this mechanism, it is unlikely that infection-blocking vaccines can be developed.

Animals↗

Periodate oxidation of R36A pneumococci greatly enhances production of hybridomas secreting anti-protein antibodies.

Most hybridomas derived from mice immunized with non-capsulated Streptococcus pneumoniae strains secrete antibodies to C-polysaccharide epitopes and very rarely against cell wall proteins. Mild periodate oxidation of the non-capsulated R36A pneumococcal strain destroys C-polysaccharide antigenicity without a noticeable loss in the immunizing capacity for proteins. Following immunization of BALB/c mice with periodate-treated R36A cells, most hybridomas obtained (87.5%) secreted anti-pneumococcal protein antibodies. This strategy can be exploited for the development of MAb to pneumococcal polypeptides which, in turn, will be of use in the analysis of pneumococcal cell wall protein antigens.

Animals↗

Ontogenic restriction of colonization of the bursa of Fabricius.

The capacity of hemopoietic precursor cells (HPC) to home to embryonic bursal and thymic grafts was investigated in embryonic and newly hatched chickens. Whereas thymic grafts developed normal histogenesis in both types of recipients, the bursal rudiment was colonized and developed in embryonic, but not in newly hatched hosts. In the latter, noncolonized bursal grafts developed neither lymphoid follicles nor granulopoiesis in the mesenchyme. These results are interpreted in terms of ontogenic "maturation" of the HPC which lose their homing potential towards the bursa while they preserve their thymic seeding capacity. This hypothesis is consistent with previously reported data which indicated cyclic continuous recruitment of the thymic lymphoid population, but restricted bursal colonization to a relatively brief period of embryonic life.

Animals↗

Complete amino acid sequence of the alpha 2 heavy chain of a human IgA2 immunoglobulin of the A2m (2) allotype.

The complete amino acid sequence of the alpha 2 heavy chain of a human IgA2 immunoglobulin of the A2m(2) allotype has been determined and is compared to the sequence of the alpha 1 chain of the human IgA1 subclass. The characteristic differences between the alpha 1 and alpha 2 chains are greatest in the hinge region and in the location and number of the oligosaccharides. Apart from the duplication in the hinge region of alpha 1 and the deletion in alpha 2, there are 23 amino acid exchanges in the constant (C) regions of the two chains. Accepted mutations are related to the surface accessibility of the residues and the proximity of carbohydrate. The results indicate that human IgA and IgG subclasses arose late in evolution and reflect similar mutationa pressures.

Amino Acid Sequence↗

Location and structural significance of the oligosaccharides in human Ig-A1 and IgA2 immunoglobulins.

The location, number, and kinds of oligosaccharides in human IgA1 and IgA2 immunoglobulins have been determined by amino acid sequence analysis of the alpha heavy chains. Both A2m allotypes of the alpha2 chain of IgA2 have two GlcN oligosaccharides that are absent in the alpha1 chain, but they lack GalN. The A2m(2) allotype has a fifth GlcN oligosaccharide. The alpha chains of IgA proteins also have subclass-specific and allotype-specific differences in amino acid sequence. Although other classes of human immunoglobulins differ in the number and kind of oligosaccharides, the sites are often homologous and are related to the immunoglobulin domain structure. Evolutionary preservation of the tripeptide acceptor sequence for GlcN probably indicates both a structural and biological role for carbohydrate.

Amino Acid Sequence↗