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Juan B De Sanctis

Publications and source records attributed to Juan B De Sanctis.

8 recordsLinked to original sources

New frontiers in the therapeutic management of transplant rejection.

Understanding of the mechanisms of transplant and xenotransplant rejection represents one of the most important aspects of both basic and clinical immunology. This review discusses the roles of 1) immune response and 2) the influence of various products of arachidonic acid metabolism on immune response in graft survival. The review also includes an overview of novel therapeutic approaches developed to prevent, or at least delay, graft rejection. New discoveries in basic and clinical immunology have generated new areas of research in pharmacology that may prevent rejection more efficiently, a key issue in modern medicine.

Animals↗

Immunophenotype characteristics of peripheral blood mononuclear leukocytes of chronic idiopathic urticaria patients.

The pathogenesis of chronic idiopathic urticaria (CIU) is not completely understood although autoimmunity has been proposed. The aim of the study was to assess the expression of different leukocyte antigens, by flow cytometry, assaying total blood of 29 patients with CIU and of 20 sex and age matched controls. Moreover, we assessed soluble CD154 a marker of immune cell activation, predominantly memory T cells. When patients were divided depending an their response to the autologous serum skin test (ASST), three different groups were encountered: group 1 (n=11): with negative ASST-, group 2 (n=11): positive ASST (ASST+) with normal lymphocyte counts and group 3 (n=7): ASST+ with low lymphocyte counts (< 1500 cells/mm3). A significant increase in CD19+ percentage and not in the absolute count (P < 0.05) was observed in group 1 as compared to controls and to the other groups. In contrast, CD30+, CD45RO+ and CD4+/CD45RO+ percentages and biologically active soluble CD154 levels were significantly higher (P < 0.05) in group 3 as compared to group 1 or to controls. In ASST positive groups, CD45RO+ and CD4+/CD45RO+ positiveness correlates with wheal diameter. In conclusion, memory cells may play a role in these different types of patients and in understanding CIU pathogenesis.

Adult↗

Interaction of immune complexes isolated from hepatitis C virus-infected individuals with human cell lines.

We investigated the interaction of immune complexes (IC) isolated from hepatitis C virus (HCV)-infected individuals with several cell lines that differentially express Fc receptors, and analyzed viral infection by the presence of HCV RNA sequences. Monocytic (U937 and Monomac-6) and lymphocytic (MOLT-4 and Jurkat) cell lines were incubated with interferon- plus phorbol myristate acetate to stimulate the expression of Fc receptors before addition of IC. Cell interaction with IC was monitored by flow cytometry. Positive cell fluorescence was detected in U937 and Monomac-6 cells [mean fluorescence intensity (MFI) 10.56+/-0.8 and 11.60+/-0.8, respectively]. Incubation of cells with monoclonal antibodies against Fc receptors for IgG before addition of IC decreased MFI in both cell lines (U937 2.1+/-0.5, Monomac-6 4.4+/-0.8, P<0.001), indicating that cell-IC interaction through these receptors was inhibited. In particular, the blockage of FcgammaRII was responsible for this effect. No binding of IC with either MOLT-4 or Jurkat cell lines was detected, which correlated with a very low Fc receptor expression. HCV RNA sequences were identified in the cells up to 120 h of post incubation with IC. These results suggest that IC can mediate entry of HCV to both U-937 and Monomac-6 cell lines mainly through the FcgammaRII.

Antigen-Antibody Complex↗

Lipoprotein lipase protects bovine endothelial cells from human NK cytotoxic activity.

Human lipoprotein lipase (LPL), in a dose dependent fashion, significantly inhibited spontaneous human natural killer (NK) cells, but not lymphokine-activated killer (LAK) cytotoxic activity against bovine pulmonary endothelial cells. The effect was dependent on endothelial heparan sulfate (HS) sites, since heparitinase reverted it. When HS is added before LPL, NK and LAK cytotoxicity are markedly reduced. Endothelial and NK cell priming, with LPL and HS+LPL, significantly induced CD40 and CD154 expression, respectively. Furthermore, CD40 expression was inversely proportional to lytic units (R2 = 0.9, P < 0.001). Treating endothelial cells simultaneously with indomethacin, CD154 fusion protein, and Wortmanin prevented the CD40 effect increasing xenograft rejection. LPL and HS+LPL protect bovine endothelial cells from NK cytotoxicity by inducing CD40, CD154 expression, and secretion of soluble factors. The high, non-modulated expression of adhesion receptors and the low number of HS sites account for the minor effect of CD40 in LAK cytotoxic responses against bovine endothelial cells.

Animals↗

CD40 and CD40L expression in the chicken embryo aorta: possible role in the endothelial-mesenchymal transdifferentiation process.

Endothelial-mesenchymal transdifferentiation (EMT) is believed to play a crucial role in embryonic vascular development and intimal thickening, which contributes to the pathogenesis of atherosclerotic lesions. However, the mechanisms by which it occurs, as well as the signals that control it, have not yet been elucidated. Given the important role played by the CD40-CD40 ligand (CD40L) system during the initiation and progress of atherosclerosis, we investigated whether both CD40 and CD40L were present in the aortic wall during EMT and the advanced stages of chicken embryo development. CD40-CD40L expression was found on endothelial cells (ECs), mesenchymal cells, and smooth muscle cells (SMCs) at all stages examined, and appeared to be distributed across the aortic wall. However, some notable differences between the expression patterns were observed. CD40 had a more restricted distribution compared to CD40L, and did not stain every cell type of the aortic wall. According to immunoblotting and enzyme-linked immunosorbent assay (ELISA) analyses, the CD40L content was highest at day 7 of development. An important and novel finding was the expression of CD40L in areas where ECs transdifferentiate into mesenchymal cells. Specifically, CD40L was associated to the surface of cells that were detaching and migrating from the monolayer of ECs, whereas for CD40 a very diffuse subcellular localization was seen at the monolayer and the detaching and migrating cells. These data suggest a possible role for CD40-CD40L interactions during EMT and the remodeling of the aorta.

Actins↗

Hypodense eosinophils: characterization of surface molecule expression.

Distinct eosinophil populations have been characterized on the basis of discontinuous Percoll density gradients. In peripheral blood, normal individuals show a low number of normodense and hypodense eosinophils, contrasting with the high amount of hypodense cells in patients who have allergies. To characterize these two eosinophil populations, we analyzed membrane expression of several antigens and cytokine receptors in normodense and hypodense eosinophils from patients who have allergies and controls. Hypodense eosinophils expressed higher levels of CD122, CD69, and CD4 in both patients with allergies and control individuals when compared to normodense eosinophils. The expression of CD125, CD124, CD25, CD132, and CD23 were similar in both cell types.

Adolescent↗

Interleukin-2 induces peroxide production by primed normodense eosinophils of patients with asthma.

In this study we assessed, by flow cytometry, the effect of interleukin 2 (IL-2) on the oxidative burst of normodense eosinophils (Eos's) isolated from 15 patients with moderately severe extrinsic asthma and 17 controls. We found that IL-2 significantly induced peroxide (H2O2) production in normodense Eos's from patients with asthma on a time kinetics study. This rise was higher in patients with immunoglobulin E levels > 180 IU/mL versus normal immunoglobulin E values. The effect of IL-2 was partially blocked by using anti-Tac antibody. In contrast, IL-2 decreased H2O2 production in normodense Eos's from controls. Cell surface expression of CD25, CD122, CD132, and CD69 were also determined and no statistical differences were found between both groups. In conclusion, IL-2 is able to increase H2O2 production by normodense Eos's isolated from patients with asthma and it may contribute to bronchial epithelium damage and chronic inflammation.

Adolescent↗

Total and biologically active serum-soluble CD154 in patients with chronic idiopathic urticaria.

The pathogenesis of chronic idiopathic urticaria (CIU) is not understood completely; however, autoimmunity has been implicated. Because membrane and soluble forms of CD154 have been reported to be increased, in several autoimmune diseases, we have quantified the soluble CD154 (sCD154) molecule by a sandwich enzyme-linked immunosorbent assay in serum samples of 32 patients with CIU (aged 32 +/- 12 years) and compared them with 32 age- and sex-matched nonallergic controls. A marked increase was observed in patients with CIU as compared with controls (4.8 +/- 2.6 ng/mL versus 2.9 +/- 0.9 ng/mL; p < 0.0005). No significant differences were found between groups of patients with positive or negative autologous serum skin test. A biological assay to determine sCD154 showed that patients with positive autologous serum skin test have the highest levels (4.9 +/- 1.2 ng/mL) of biologically active sCD154 as compared with their negative counterparts (2.2 +/- 1.3 ng/mL; p < .001) and controls (0.6 +/- 0.3 ng/mL; p < 0.001). Active sCD154 can be derived from mast cell activation or other leukocytes. It is concluded that active sCD154 may be involved in the immune activation observed in patients with CIU.

Adult↗