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Biomedical subjects

L Baranda

Publications and source records attributed to L Baranda.

At least 19 recordsLinked to original sources
PubMed2002

Effect of arsenic, cadmium and lead on the induction of apoptosis of normal human mononuclear cells.

The aim of this work was to investigate the effect of cadmium, lead and arsenic on the apoptosis of human immune cells. Peripheral blood mononuclear cells (MNC) were incubated with increasing concentrations of these metals and then cellular apoptosis was determined by flow cytometry and by DNA electrophoresis. We found that arsenic induced a significant level of apoptosis at 15 microM after 48h of incubation. Cadmium had a similar effect, but at higher concentrations (65 microM). In addition, cadmium exerted a cytotoxic effect on MNC that seemed to be independent of the induction of apoptosis. In contrast, concentrations of lead as high as 500 microM were nontoxic and did not induce a significant degree of apoptosis. Additional experiments showed that arsenic at concentrations as low as 1.0 microM had a significant pro-apoptotic effect when cells were cultured in the presence of this pollutant for more than 72. Non-T cells were more susceptible than T lymphocytes to the effect of arsenic and cadmium. Interestingly, MNC from children chronically exposed to arsenic showed a high basal rate of apoptosis and a diminished in vitro sensibility to this metalloid. Our results indicate that both arsenic and cadmium are able to induce apoptosis of lymphoid cells, and suggest that this phenomenon may contribute to their immunotoxic effect in vivo.

Adult↗
PubMed2000

Co-stimulatory signals increase the reactivity of gammadelta T cells towards mycobacterial antigens.

Although it has been shown that gammadelta T lymphocytes are able to react with different cell-associated or soluble antigens, the immune repertoire of these cells appears to be skewed to the recognition of mycobacterial antigens. We have studied the number and reactivity of gammadelta T cells towards several mycobacterial antigens in patients with tuberculosis and leprosy, as well as their healthy contacts and control individuals. We found an increased number of Vdelta2+ cells in healthy contacts (PPD+ and lepromin+) and tuberculoid leprosy patients. The gammadelta T cells from lepromatous leprosy showed a decreased response to all antigens tested, but some of these patients exhibited a significant response to the 30-kD glycoprotein of Mycobacterium tuberculosis. Interestingly, the reactivity of gammadelta T cells against mycobacterial antigens was significantly increased by costimulatory signals generated through CD7, LFA-1, CD50 and CD69 in all groups. However, signalling through CD69 did not enhance the responsiveness of gammadelta lymphocytes from lepromatous patients. On the other hand, the in vitro blockade of IL-10 with a specific antibody enhanced the cell proliferation of gammadelta lymphocytes from lepromatous leprosy patients, whereas exogenous IL-10 had an opposite effect in most individuals studied. These results suggest the potential role of different cell membrane receptors in the regulation of gammadelta T cell proliferation induced by mycobacteria, as well as the possible involvement of IL-10 in this phenomenon.

Antibodies, Monoclonal↗
PubMed1999

Presence of activated lymphocytes in the peripheral blood of patients with halo nevi.

BACKGROUND: The involution of the central pigmented lesion in halo nevus (HN) seems to be mediated by an immune response against self antigens expressed by melanocytes. OBJECTIVE: We assessed the presence of activated lymphocytes in the peripheral blood lymphocytes from patients with HN. METHODS: Peripheral blood was obtained from patients with HN associated with benign pigmented lesions (5) or melanoma (2) as well as from patients with melanoma without HN (5) and healthy subjects (10). Activated lymphocytes were detected by flow cytometry analysis using monoclonal antibodies (mAb) against CD69, CD71, CD98, HLA-DR, and activated beta(1) integrins (HUTS-21 mAb). RESULTS: The peripheral blood lymphocytes from patients with HN, associated with either benign or malignant lesions, exhibited a significantly higher expression of all activation markers studied compared with patients with melanoma without HN or compared with healthy subjects. Therefore the peripheral blood of HN patients contained a significant fraction of lymphocytes with an activated (CD69(+), HLA-DR(+), CD98(bright)), cell proliferating (CD71( bright)), and high adhesive (HUTS-21(bright)) phenotype. These activated cells disappeared from peripheral blood after the surgical resection of the skin lesion. CONCLUSION: Our findings further support the involvement of immune activation in HN phenomenon.

Adolescent↗
PubMed1998

Pentoxifylline inhibits adhesion and activation of human T lymphocytes.

We have herein studied the effect of pentoxifylline (PTX) on the adhesion and activation of human T lymphocytes. We found that PTX inhibited the adhesion of T cells to the beta1 and beta2 integrin ligands VCAM-1 and ICAM-1; this inhibitory activity was dose dependent, with a maximal effect from 12 to 24 h. We also found that PTX was able to interfere with the activation of beta1 integrins induced by intracellular signals; however, the conformational change of beta1 integrins induced by extracellular stimuli (e.g., activating mAbs, or Mn2+) was not significantly affected by this drug. In addition, the homotypic aggregation of T cells induced by anti-beta1 and -beta2 integrin chain mAbs was also inhibited by PTX. PTX had a significant inhibitory effect on the T lymphocyte expression of the activation Ags CD25 (IL-2R alpha-chain), CD69 (activation-inducer molecule), and CD98 (4F2) induced by PHA. Accordingly, PTX also interfered with early cell activation events such as the rise in intracellular Ca2+ and the activation of the Na+/H+ antiporter induced by PHA and phorbol esters, respectively. Furthermore, this drug inhibited both the cell cycle progression and cell proliferation of T cells induced through the CD3/TCR complex. However, this drug did not show any effect on the cell activation/proliferation induced by PMA plus ionomycin. Our results indicate that PTX interferes efficiently with the activation and cell adhesion of human T lymphocytes. These effects may be of relevance for the clinical uses of this drug.

Cell Adhesion↗
PubMed1998

Penetrating anti-DNA monoclonal antibodies induce activation of human peripheral blood mononuclear cells.

Different studies have shown that some autoantibodies are able to penetrate into living cells and that this phenomenon has functional consequences, including apoptosis. We have explored the effect of anti-DNA antibodies (Ab) on the in vitro activation of peripheral blood mononuclear cells (PBMNC) and found that a human polyclonal anti-DNA, IgG, which efficiently penetrated living cells, was able to induce the expression of different cell activation antigens in vitro such as CD69, CD71 or CD98 by PBMNC from normal individuals. However, the cell activation phenotype induced by anti-DNA Ab was considered anomalous since the expression of some activation antigens was not up-regulated, and others showed aberrant behaviour (such as down-regulation of ICAM-1 expression). Similar results were obtained using different murine anti-DNA monoclonal antibodies (mAb). In addition, mAb that showed an efficient ability to penetrate living cells tended to have a greater effect on PBMNC activation. Anti-DNA Ab were also able to induce a noticeable expression of CD95/Fas. These data indicate that penetrating anti-DNA Ab are able to induce an anomalous activation state in vitro in a significant fraction of PBMNC. We believe this effect may occur in vivoand could have an important function in the pathogenesis of the immune dysregulation seen in SLE.

Animals↗
PubMed1998

Role of IL-10 in the abnormalities of early cell activation events of lymphocytes from patients with systemic lupus erythematosus.

Lymphocytes from patients with systemic lupus erythematosus (SLE) exhibit abnormalities in early cell activation events as well as increased production of IL-10. We explored the possible role of IL-10 on defective cell activation events of SLE lymphocytes and first studied the in vitro effect of IL-10 on peripheral blood mononuclear cells (PBMNC) from healthy subjects. After 5 days of culture in the presence of exogenous IL-10, these cells demonstrated abnormal expression of CD69 as well as high intracellular pH and defective activation of the Na+/H+ anti-porter by PMA. We then investigated the effect of IL-10 blockade on PBMNC from SLE patients. SLE PBMNC cultured for 5 days with a blocking anti-IL-10 monoclonal antibody (mAb) partially corrected abnormalities in CD69 expression and intracellular pH; however, in 1/5 patients studied, no significant positive effect was observed. The effect of the anti-IL-10 mAb was apparently not related to protection against activation-induced cell death. We conclude that IL-10 in normal PBMNC induce some of the defects in early cell activation events seen in SLE lymphocytes. Accordingly, the blockade of IL-10 partially corrects these abnormalities in SLE cells. Our data further support the importance of IL-10 in immune dysfunction seen in SLE.

Antibodies, Monoclonal↗
PubMed1998

Stimulation through CD50 preferentially induces apoptosis of TCR1+ human peripheral blood lymphocytes.

Apoptosis has an important role in several key immunological phenomena such as regulation of the immune response, and deletion of auto-reactive cells. This phenomenon is induced following the interaction of several cell membrane receptors with their respective ligands or after cell activation. We have studied the possible effect of signaling through CD50/ICAM-3 and CD69/AIM on apoptosis of peripheral blood lymphocytes. Apoptosis was assessed by both flow cytometry analysis (content of cell DNA and binding to annexin V), and detection of DNA fragmentation by agarose gel electrophoresis. We found that a stimulatory anti-CD50 mAb was able to induce a small but significant degree of apoptosis in resting peripheral blood mononuclear cells from most donors; this effect was dose-dependent and was evident as early as at 12 h, with a maximal induction at 48 h. Studies with T and non-T cells showed that only the former cell population was sensitive to the induction of apoptosis through CD50. Further experiments revealed that the anti-ICAM-3 mAb preferentially induced apoptosis of TCR gamma delta-bearing cells. In addition, we found a significant increase in Cai2+ in PBMC stimulated with an anti-CD50 mAb, suggesting the involvement of this signaling pathway in the induction of apoptosis through this adhesion receptor. In contrast, under our experimental conditions, stimulation through CD69 did not have any effect on the induction of apoptosis on either cultured T lymphoblasts or PMA-stimulated PBMC. Our findings suggest that the interaction of CD50 with its natural ligand LFA-1 results in the induction of apoptosis in a significant fraction of resting PBMC. This phenomenon may be involved in immune regulation, lymphocyte turnover and peripheral deletion of auto-reactive cells.

Antibodies, Monoclonal↗
PubMed1997

Profile of cytokine mRNA expression in spontaneous and UV-induced skin lesions from actinic prurigo patients.

BACKGROUND: Actinic prurigo (AP) appears to be an immune-mediated disease triggered by exposure to ultraviolet light (UV). OBJECTIVE: To assess the profile of cytokine production in skin lesions from AP patients. METHODS: The cytokine production (IL-1 beta, IL-2, IL-4, IL-6, IL-10, IL-13, TNF-alpha, IFN-tau, and TGF-beta) in skin biopsies from 12 AP lesions was determined by a semiquantitative coupled reverse transcription-polymerase chain reaction. RESULTS: We found expression of TGF-beta and IL-13 genes in most AP skin lesions; IL-1 beta, IL-6, TNF-alpha, IFN-tau, and IL-10 were detected in some of these specimens. However, the levels of expression of all cytokines studied were not significantly different in AP skin lesions compared to nonlesional skin. CONCLUSIONS: TGF-beta and IL-13 might have a key role in both the inflammatory phenomenon and absence of significant expression of most cytokines in AP skin. The cytokine production in AP skin resembles that observed in rheumatoid synovium, a paucity in cytokine expression despite the presence of infiltrating activated mononuclear cells.

Adolescent↗
PubMed1997

Involvement of cell adhesion and activation molecules in the pathogenesis of erythema dyschromicum perstans (ashy dermatitis). The effect of clofazimine therapy.

OBJECTIVES: To assess the expression of several cell adhesion and lymphocyte activation molecules in erythema dyschromicum perstans lesions, and to evaluate the effect of clofazimine therapy on the expression of these molecules. DESIGN AND METHODS: A prospective study. Skin biopsy samples were obtained from patients before and after 3 months of clofazimine therapy, and the expression of cell adhesion and activation molecules was assessed by an immunohistochemical technique. SETTING: This study was performed in a clinical referral center and an immunology research laboratory. PATIENTS: We studied 6 patients with erythema dyschromicum perstans. A diagnosis was made on the basis of clinical and histological criteria. Two patients discontinued participation in the study: one because of adverse effects and the other for unknown reasons. INTERVENTIONS: Patients were treated with clofazimine, 100 mg/d, for 3 months. MAIN OUTCOME MEASURES: Expression of cell adhesion and lymphocyte activation molecules in skin biopsy specimens before and after clofazimine therapy. RESULTS: Before clofazimine therapy, we detected a noticeable expression of intercellular adhesion molecule 1 and major histocompatibility complex class II molecules (HLA-DR) in the keratinocyte basal cell layer. In addition, CD36, a thrombospondin receptor that is not expressed by normal skin, was detected in the strata spinosum and granulosum. The dermal cell infiltrate expressed the activation molecule AIM/CD69 and the cytotoxic cell marker CD94. After clofazimine therapy, the expression of intercellular adhesion molecule 1 and HLA-DR disappeared, as well as the mononuclear cell infiltrate. CONCLUSIONS: Our results suggest that some cell adhesion and activation molecules are involved in the pathogenesis of erythema dyschromicum perstans. Clofazimine appears to have an important effect on the inflammatory phenomenon of erythema dyschromicum perstans.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Autoeczematization is associated with abnormal immune recognition of autologous skin antigens.

BACKGROUND: The pathogenesis of autoeczematization (AE) is not well understood; however, previous studies suggest that AE is an autoimmune condition. OBJECTIVE: Our purpose was to assess whether AE is associated with an abnormal immune recognition of autologous skin antigens. METHODS: Eight patients with AE, six healthy control subjects, and three patients with localized contact dermatitis (LCD) were studied. Activation markers were detected on peripheral blood T lymphocytes. Autologous mixed epidermal cell-lymphocyte reaction (AMECLR) was performed for each subject and cell proliferation was assessed by tritiated thymidine incorporation. RESULTS: Many activated T cells were detected in patients with AE (5.2% +/- 4.5% vs 0.2% +/- 0.4% in control subjects, p < 0.05). AMECLR showed a significantly higher cell proliferation in AE compared with both healthy subjects and patients with LCD (6372 +/- 3217 cpm vs 2638 +/- 1788 cpm, and 2471 +/- 1389 cpm, respectively; p < 0.05). Peripheral blood mononuclear cells cultured in the presence of an autologous skin homogenate also showed a significantly increased cell proliferation in patients with AE than in control subjects. CONCLUSION: Our results suggest that an abnormal immune response against autologous skin antigens occurs in AE that could be related to the pathogenesis of this disease.

Autoantigens↗
PubMed1993

Lack of expression of intercellular adhesion molecule ICAM-1 in lepromatous leprosy patients.

It is conceivable that an abnormal expression of cell-adhesion molecules can contribute to the poor inflammatory response seen in some inflammatory skin diseases. Adhesins are cell-surface molecules that are expressed by many cell types. The main function of adhesins appears to be the promotion of cellular interactions, such as those occurring between immune cells. The epidermis of patients with inflammatory skin diseases exhibits an increased expression of ICAM-1, and it has been postulated that such increased expression can be important in the genesis of cutaneous inflammation. The expression of cell-adhesion molecules (LFA-1, LFA-2, LFA-3 and ICAM-1) in skin lesions of leprosy patients was studied, as well as the in vitro expression of these molecules induced with gamma interferon (IFN-gamma). A lack of expression of ICAM-1 in the epidermis of lepromatous patients was noted; in addition, no expression of ICAM-1 was seen in the nearly normal skin from these patients incubated with IFN-gamma. A similar expression of the four molecules studies was noted in the dermis of both the lepromatous and tuberculoid types of leprosy. The epidermis of the lepromatous leprosy patients appears to have a defective expression of ICAM-1.

Antigens, CD↗
PubMed1991

Immune sensitization against epidermal antigens in polymorphous light eruption.

To get further insight into the pathogenesis of polymorphous light eruption, we studied nine patients with polymorphous light eruption and six healthy persons. Two skin biopsy specimens were obtained from each person, one from previously ultraviolet light-irradiated skin and another one from unirradiated skin. An epidermal cell suspension, skin homogenate, or both were prepared from each specimen. Autologous cultures were made with peripheral blood mononuclear cells combined with irradiated or unirradiated skin homogenate and peripheral blood mononuclear cells combined with irradiated or unirradiated epidermal cell suspension. Cell proliferation was assessed by 3H-thymidine incorporation assay. The response of peripheral blood mononuclear cells to unirradiated epidermal cells or unirradiated skin homogenate was similar in both patients and controls. However, peripheral blood mononuclear cells from patients with polymorphous light eruption showed a significantly increased proliferative response to both irradiated epidermal cells and irradiated skin homogenate. Our results indicate that ultraviolet light increases the stimulatory capability of polymorphous light eruption epidermal cells in a unidirectional mixed culture with autologous peripheral blood mononuclear cells. This suggests that an immune sensitization against autologous ultraviolet light-modified skin antigens occurs in polymorphous light eruption.

Adolescent↗
PubMed1988

Evidence of cell-mediated immune contrasuppression in lepromatous leprosy: modulation of a putative T contrasuppressor cell-subset.

Some lepromatous leprosy (LL) patients are characterized by the presence of activated suppressor T cells that specifically inhibit the immune response to Mycobacterium leprae antigens. Immune contrasuppressor (CS) cell activity antagonize suppressor function. Whereas the former function has been extensively studied in leprosy, the latter has not been explored. We studied the peripheral blood mononuclear cells (PBMNC) of 20 patients with leprosy (10 lepromatous and 10 tuberculoid) and six healthy contacts. We found CS-like activity in the PBMNC from some LL patients when assayed in vitro using lepromin as antigen. This CS-like function was found in CD8+, vicia villosa adherent (VV+) T cells. CS-like activity was not detected in PBMNC from either tuberculoid patients or healthy contacts. Pre-treatment of CD8+, VV+ cells with either recombinant IL-2 (5 u/ml) or recombinant interferon-gamma (1,000 u/ml) did not modify significantly their putative CS function. However, in 50% of lepromatous patients the pre-incubation of CD8+, VV+ cells with both lymphokines together increased significantly the CS-like activity. These data suggest that the in vitro immune response to M. leprae in some LL patients can be augmented by either modifying numerically the contrasuppressor T cells or activating them with lymphokines.

Antigens, Bacterial↗
PubMed1987

Quantitative analysis of contrasuppressor T lymphocytes in leprosy; induction of Ia antigens with gamma interferon.

Lepromatous leprosy is characterized by immune anergy and abnormal suppressor T-cell function. Contrasuppressor cells are a subset of CD8+, vicia villosa-adherent T lymphocytes. T-contrasuppressor (Tcs) cells act on T-helper cells to cause them to become unresponsive to the action of T-suppressor cells. In 8 lepromatous (LL) and 7 tuberculoid (TT) patients, and 6 healthy contacts we studied the percent of the following lymphocyte subsets: CD3+, CD4+, CD8+, Ia+, vicia villosa+ (VV+), CD8, VV+, VV, Ia+, and Ia, Tac+. This was done in baseline status as well as post-stimulation with recombinant gamma interferon (rIFN-gamma). We found that peripheral blood mononuclear cells from LL and TT patients and controls exhibit a similar number of putative contrasuppressor lymphocytes (CD8, VV+ cells). However, in the contrasuppressor subset from LL patients we found a low percent of Ia+ (p less than 0.05 compared to controls or TT). In the three groups studied, the rIFN-gamma enhanced the percent of Ia+ lymphocytes in the CD8, VV+ cell subpopulation. However, the CD8, VV+ lymphocytes from LL patients, despite the effect of rIFN-gamma, continue to have a low percent of Ia+ cells (p less than 0.05 compared to controls or TT). These findings suggest that LL patients might have abnormalities in the contrasuppressor immune circuit. Future functional studies on the role of Tcs cells in the anergy seen in LL will be required in order to define the apparent dysfunction occurring in this disease.

Antigens, Surface↗