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Biomedical subjects

L Villa

Publications and source records attributed to L Villa.

At least 91 records · Page 5Linked to original sources
PubMed1988

IgA-driven antibacterial activity against Streptococcus pneumoniae by mouse lung lymphocytes.

To investigate the role of lung lymphocytes (LL) in the local defense mechanisms, we studied the natural antibacterial (NA) activity of mouse LL with an in vitro assay using S. pneumoniae type 3 as target. In parallel, natural killer (NK) activity against YAC-1 tumor cells was investigated. Lung cells obtained by enzymatic digestion were found to exert detectable NA and NK activities, which were further increased after purification of LL (greater than 90% lymphocytes) by carbonyl iron and magnet treatment. Depletion experiments with antibodies and complement indicated that the effector cell of NA activity was a Thy 1.2+, L3T4+, aGM1+ lymphocyte, whereas the effector of NK activity was found to have a Thy 1.2-, aGM1+ phenotype. Preincubation of LL with anti-IgA antibodies, but not with anti-IgG, completely inhibited NA activity, suggesting that it was mediated by preexisting IgA bound to the LL surface. Furthermore, purified IgA from S107 plasmacytoma with specificity for phosphorylcholine, a component of the outer wall of S. pneumoniae, was able to enhance the antibacterial activity of LL and to restore their activity after treatment with anti-IgA. In addition, S107 antibodies were found to specifically induce antibacterial activity against S. pneumoniae in resident alveolar macrophages (AM) and peritoneal exudate cells, which did not express NA activity. We conclude that mouse LL include a subset of IgA-bearing lymphocytes with the phenotype of helper-T cells, which are able to exert NA activity against pneumococcus through an IgA-driven mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

A prospective study of the clinical benefits of prostacyclin in 554 cardiopulmonary bypass procedures.

Abnormal bleeding after cardiopulmonary bypass (CPB) may result from incomplete neutralization of heparin, increased fibrinolytic activity, consumption of coagulation factors, or from a reduction in the number of circulating platelets together with impairment of platelet function. Although researchers have reason to believe that hemostasis after CPB could be improved with prostacyclin (PGI(2)), a potent inhibitor of platelet aggregation, the drug's clear-cut benefits in this respect have not yet been confirmed. After conducting an initial study concerning the fate of platelets during CPB, in which we determined that PGI(2) had a protective effect, we investigated the effects of PGI(2) infusion during CPB on postoperative blood loss in 554 open-heart surgery patients, 200 of whom underwent valve replacement, 200 of whom had coronary artery bypass grafting (CABG), and 154 of whom underwent repeat valve replacement or CABG. The patients were divided into 2 groups: 277 patients (the study group) received both heparin and PGI(2) during CPB, whereas the remaining 277 patients (the control group) were given heparin alone. Of the patients who underwent surgery for the first time, those treated with PGI(2) had a reduced mean blood loss (p < 0.05 only in CABG patients) in comparison with those who received heparin alone. Of the patients who underwent redo operations, those who received PGI(2) had a nonsignificant tendency toward reduced blood loss. The mean difference in blood loss between the study group and the control group had no clinical relevance, however, because it was less than the smallest practical unit of measurement (i.e., 1 unit of blood).

Journal Article↗
PubMed1987

In vivo immunostimulating activity of the 163-171 peptide of human IL-1 beta.

The stimulating effect of a synthetic nonapeptide (fragment 163-171) of human interleukin 1 beta (IL-1 beta) on antibody responses to both T helper-dependent and T helper-independent antigens was investigated. It was shown that the nonapeptide enhanced the antibody response, as evaluated in the hemolytic plaque assay, of spleen cells from mice immunized with sheep red blood cells (SRBC). The activity of the 163-171 peptide on the primary response to SRBC was dose-dependent, being maximal when the peptide was inoculated at 100 mg/kg together with the antigen. Moreover, the 163-171 peptide was also effective in enhancing the secondary response to SRBC. The effect of the 163-171 peptide was to augment the frequency of cells specific for the antigen, inasmuch as no increase was ever observed in spleen cell numbers after treatment. In all these studies, human recombinant IL-1 beta gave effects qualitatively comparable to those of the 163-171 peptide, with a maximal activity at 20 ng/kg. Both the 163-171 peptide and human recombinant IL-1 beta were also able to enhance the in vivo immune response to a T helper-independent antigen such as SIII, a poorly immunogenic polysaccharidic antigen from Streptococcus pneumoniae type III. It can therefore be proposed that this synthetic nonapeptide of human IL-1 beta may represent a good candidate for use as adjuvant in vaccines.

Adjuvants, Immunologic↗
PubMed1987

Adjuvant activity of the 163-171 peptide of human IL-1 beta administered through different routes.

The synthetic peptide VQGEESNDK, corresponding to the fragment 163-171 of human IL-1 beta, could potently enhance the primary and secondary response of mice immunized with SRBC, measured as the number of specific antibody-secreting cells in the spleen. This adjuvant activity was dose-dependent, being maximal when the nonapeptide was administered intraperitoneally (i.p.) or subcutaneously (s.c.) at 100 mg/kg or orally (p.os) at 33 mg/kg, reaching levels comparable to those attained by 20 ng/kg of hu rIL-1 beta given i.p. or s.c. A dose-dependent enhancement of the primary response to SRBC was also observed when IL-1 beta or its peptide fragment were injected intravenously (i.v.) together with the antigen, with a maximum activity at 10 micrograms/kg for the 163-171 peptide and 100 pg/kg for hu rIL-1 beta. Thus, the in vivo immunostimulatory activity of hu IL-1 beta depended on the administration route as follows: i.v. much greater than s.c. = i.p. much greater than p.os. Conversely, the adjuvant effect of the 163-171 peptide was: i.v. much greater than p.os greater than s.c. = i.p.

Adjuvants, Immunologic↗
PubMed1986

A short synthetic peptide fragment of human interleukin 1 with immunostimulatory but not inflammatory activity.

Short peptide fragments of human and murine interleukin 1 (IL 1) were synthesized on the basis of their predicted exposure on the surface of the molecule in an attempt to identify the minimal structure responsible for the immunostimulatory activity of IL 1. One of these peptides, a fragment of nine residues of human IL 1 beta (VQGEESNDK, fragment 163-171), showed high T cell activation capacity, as judged by its ability to stimulate murine thymocyte proliferation and to potently induce interleukin 2 production in spleen cells. On the other hand, the 163-171 peptide was devoid of prostaglandin-inducing capacity in vitro and pyrogenic activity in vivo, two inflammatory features peculiar to the entire hu IL 1 beta molecule. Thus we propose that this peptide may represent one of the portions of hu IL 1 beta responsible for its immunostimulatory capacity.

Amino Acid Sequence↗
PubMed1986

IgA-driven T cell-mediated anti-bacterial immunity in man after live oral Ty 21a vaccine.

Cellular immunity against Salmonella typhi was observed by using a direct anti-bacterial in vitro assay in volunteers orally vaccinated with the live S. typhi mutant strain Ty 21a. With this experimental approach, it was demonstrated that Ty 21a vaccine also induces cellular immunity against S. paratyphi A and B. Interestingly, the mechanism involved in cellular immunity against bacteria seems to be of an antibody-dependent cellular cytotoxicity (ADCC) type, with IgA acting as the humoral arm and CD4+ T lymphocytes as the cellular one. In accordance with the increase in IgA-driven ADCC against S. typhi, a major rise in IgA against O and H antigens was observed in the serum of vaccinees in parallel to an increase in IgG of identical specificity. Furthermore, a Ty 21 vaccine induced cellular activity against flagellar antigens. These results indicate that IgA-ADCC by T lymphocytes against bacteria can originate from local stimulation of the gut mucosal immune system. This cellular defense mechanism might be at the origin of the protection induced by Ty 21a vaccine.

Administration, Oral↗
PubMed1986

Calmodulin-like protein from Bacillus subtilis.

The first example of a calmodulin-like activity in a Gram-positive bacterium, Bacillus subtilis, is reported. A calcium ion-dependent, 3', 5' cyclic-AMP phosphodiesterase-stimulating activity was found in the soluble fraction of cell-free extracts of cells sporulating in a chemically-defined medium; activation was reversed by trifluoperazine. The activity was heat stable, bound to phenothiazine-agarose in a calcium ion-dependent manner and was eluted therefrom with buffer containing EGTA, and displaced authentic beef brain calmodulin from its antibody in a radioimmunoassay.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Inhibition of proliferation of human leukaemic cell populations by deferoxamine.

Deferoxamine is a hydroxylamine which binds ferric ions to form a highly stable complex. Since iron is thought to be required at a critical stage for cell proliferation, we investigated the effect of deferoxamine on the proliferative activity of human leukaemic cell populations in vitro by means of 3 permanent cell lines, HL60, U937 and 8402. We found deferoxamine to be a potent inhibitor of DNA synthesis and proliferation of leukaemic cells, acting by accumulating treated cells at the early S phase of the cell cycle. Suppression of leukaemic proliferation was obtained at deferoxamine concentrations in the range usually achieved in the treatment of patients for iron overload. Deferoxamine might therefore warrant further investigation as a potentially useful agent for leukaemia chemotherapy.

Cell Division↗
PubMed1985

Modulation of in vitro natural cell-mediated activity against enteropathogenic bacteria by simple sugars.

Lymphoid cells from mouse Peyer's patches and spleens were tested in a 2-h in vitro assay for their natural activity against the enteropathogenic bacteria Salmonella typhimurium, Salmonella enteritidis, Salmonella tel aviv, and Shigella sp. X16. The antibacterial activity expressed by normal cells was detected against all the bacterial strains tested with the exception of Peyer's patch lymphocytes against S. tel aviv and splenocytes against Shigella sp. X16. To determine whether the different expression of natural antibacterial activity might be due to lectin-like proteins interacting with the saccharidic moieties of the bacterial wall, 11 simple sugars were preincubated with the effector cells before the in vitro assays. We found that some of them could block the natural antibacterial activity as well as induce antibacterial activity when this was not spontaneously expressed. Interestingly, a different panel of sugars among those employed was observed to affect the antibacterial activities for each of the above-mentioned bacterial targets and each effector cell. However, the same panel of sugars was able to block or stimulate the lymphocyte activity when bacteria with the same somatic antigens as two substrains of S. typhimurium and one strain of Salmonella schottmuelleri were employed. To further investigate the interaction between effector cells and bacteria, effector cells or Shigella sp. X16 targets were treated with proteolytic, glycolytic, and lipolytic enzymes before the in vitro assays. Furthermore, EDTA was used to analyze the role of divalent cations in this experimental system. The results obtained suggest that lectin-like proteins playing a role in this interaction are present not only on lymphocytes but also on bacteria and that divalent cations are essential for the expression of in vitro antibacterial activity.

Animals↗