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Biomedical subjects

G Virella

Publications and source records attributed to G Virella.

At least 91 records · Page 5Linked to original sources
PubMed1989

The potentiation of B lymphocyte responses through CD2/LFA-3 interactions involving erythrocytes is IL2 independent.

The response of human B cells to pokeweed mitogen (PWM) stimulation is potentiated when autologous erythrocytes (E) are added to peripheral blood mononuclear cell (PBMC) cultures. This potentiation has been previously shown to be dependent on interactions between the CD2 molecule on T cells and the lymphocyte function-associated antigen 3 (LFA-3) expressed by autologous erythrocytes. Since in other experimental systems the activation of T cells by CD2/LFA-3 interactions has resulted in increased secretion of interleukin 2 (IL2), we were interested in studying the role of IL2 in PBMC cultures stimulated with PWM and autologous E. The addition of autologous E significantly depressed IL2 levels in PWM-stimulated PBMC cultures. This effect was not secondary to increased expression of IL2 receptors by activated cells, since the addition of anti-TAC antibodies did not result in a significant increase in measurable levels of IL2. The addition of anti-IL2 to PBMC failed to abrogate the potentiating effect of E and it actually further enhanced the production of IgM and IgG from cultures stimulated with PWM + E. These results suggest that the potentiation of B cell function induced by autologous E is not mediated by IL2, either directly or indirectly. It is possible that the effect of autologous E either is mediated by other interleukins or is dependent on cell-to-cell contact with directed release of IL2 and/or other lymphokines without detectable secretion to the extracellular compartment.

Antigens, CD↗
PubMed1989

Depression of humoral responses and phagocytic functions in vivo and in vitro by fish oil and eicosapentanoic acid.

Previous studies have demonstrated that eicosapentanoic acid (EPA) has anti-inflammatory properties in both humans and experimental animals and may also depress humoral immunity in experimental animals. Our investigations showed that the addition of eicosapentanoic acid to human peripheral blood mononuclear cell cultures inhibited B cell responses to mitogenic stimulation and depressed the expression of interleukin 2 receptors in pokeweed mitogen-stimulated lymphocytes. Neutrophils were also affected in their ability to release the contents of primary and secondary granules, particularly when stimulated with antigen-antibody complexes. Similar depressions of B cell responses and neutrophil functions were observed in a normal volunteer who ingested 6 g/day of a commercially available fish oil extract (equivalent to 2.1 g of EPA/day) during a 6-week period. Phagocytosis, enzymatic release, circulating immunoglobulin levels, and the response to tetanus toxoid both in vivo and in vitro were depressed during ingestion of fish oil. Most parameters showed a trend toward normalization 6 weeks after the suspension of fish oil supplementation. These effects of fish oil extracts and EPA on phagocytosis and humoral responses may be advantageously used in the therapy of chronic inflammatory diseases and autoimmune diseases but could be a cause for concern when these compounds are used for longer periods of time and with minimal medical supervision for the prophylaxis of atherosclerosis.

Antibody Formation↗
PubMed1988

The interaction of CD2 with its LFA-3 ligand expressed by autologous erythrocytes results in enhancement of B cell responses.

The addition of autologous erythrocytes to unfractionated human mononuclear cell cultures results in enhancement of B cell responses to antigens and mitogens. This costimulating effect of red cells is abrogated by their preincubation with anti-LFA-3 monoclonal antibody. Preincubation of mononuclear cells with anti-CD2 monoclonal antibodies (anti-Leu 5b, OKT11, used singly) has a down-regulating effect on B cell activation and no enhancement of B cell responses is seen when red cells are added to anti-CD2-treated cultures. These results demonstrate a functional effect on B cells of the interaction between the CD2 molecule on T lymphocytes and its natural ligand, LFA-3. The precise mechanism by which this costimulating effect on B lymphocytes takes place is unclear. The study of T cell populations and T cell activation markers shows that the addition of erythrocytes causes a small but reproducible increase in the number of cells expressing the IL-2 receptor and the addition of IL-2 enhances the response of mononuclear cells to antigenic stimulation in the presence of erythrocytes. However, the supernatants of mononuclear cell cultures stimulated with pokeweed mitogen in the presence of autologous erythrocytes show decreased levels of IL-2, compared to supernatants of cells stimulated with pokeweed mitogen alone. The same supernatants show increased levels of interferon-gamma, but the addition of this lymphokine to cultures stimulated with pokeweed mitogen has no potentiating effect. It is possible that the effect of erythrocytes is mediated by other growth and/or differentiation factors, and additional studies will be required to clarify this point.

Antibodies, Monoclonal↗
PubMed1988

Depression by Fc gamma receptor ligands of SRBC-induced IgM-PFC generation in human blood mononuclear cell cultures.

A tissue-culture system to stimulate human peripheral blood mononuclear cells (PBMC) has been employed in which IgM plaque-forming cell (IgM PFC) generation in response to sheep erythrocytes (SRBC) is dependent on macrophages and T suppressor and helper lymphocytes. In this system PBMC from normal subjects give IgM PFC responses ranging from 26 to 938 PFC/culture. Heat-aggregated human IgG or immune complexes present for the duration of culture induce a significant depression of PFC. Unaggregated IgG has no effect on the response or only a moderate stimulatory effect at the highest dose. The results of these experiments are compatible with previous results in a murine system, which indicated that Fc gamma receptor-positive (Fc gamma R+) cells in the suppressor subset are the target for aggregated IgG and induce depression of the PFC response. A similar mechanism may be operating in the human system described here, although the target cell has not been identified. These results may reflect a mechanism of immunomodulation dependent on interaction of Fc receptor (FcR) ligands with FcR, which may play a role in the pathogenesis of immune complex disorders.

Antibody-Producing Cells↗
PubMed1988

Mononuclear cells from rheumatoid arthritis patients exhibit a depressed IgM response to sheep erythrocyte stimulation in vitro.

Human peripheral blood mononuclear cells when cultured for the short term (11 days) produce an optimal IgM plaque-forming cell (PFC) response to sheep erythrocytes, which is dependent on macrophages and T suppressor and helper lymphocytes. With this system we have investigated the PFC response of individuals with rheumatoid arthritis and compared this to the response of normal sex- and age-matched controls and of patients with osteoarthritis. The response of rheumatoid arthritis patients was significantly lower than that of subjects in the other two categories.

Animals↗
PubMed1987

Human endothelial cell damage induced by interactions between polymorphonuclear leukocytes and immune complex-coated erythrocytes.

We have examined, in vitro, the effects of autologous erythrocytes (RBC) coated with soluble immune complexes (RBC-IC) on the interactions of polymorphonuclear leukocytes (PMN) with human endothelial cell (EC) cultures. RBC-IC were prepared by incubating human RBC with soluble immune complexes, prepared with keyhole limpet hemocyanin (KLH) and rabbit anti-KLH in antigen excess, using normal human serum as a complement source. Several parameters believed to be related to EC-PMN interactions, including adherence of PMN to EC, detachment of EC after incubation with media harvested from RBC-IC-stimulated PMN, and the release of 2-deoxy-D-[3H]glucose from damaged EC, were investigated. The proportion of PMN adhering to EC increased in direct proportion to the number of RBC-IC used to stimulate PMN. Media harvested from PMN stimulated with RBC, RBC incubated with complement, RBC-IC, or opsonized zymosan caused variable degrees of detachment of cultured EC. The percentage of EC detached was directly related to the intensity of the PMN degranulation as measured by lysozyme release with a correlation coefficient of 0.935, comparing the natural log of the lysozyme released to the percentage EC detachment. Finally, RBC-IC added to PMN and EC induced PMN-mediated EC damage as measured by the release of 2-deoxy-D-[3H]glucose from the labeled EC. The release of 2-deoxy-D-[3H]glucose from the labeled EC was directly related to the number of RBC-IC used to stimulate the PMN. These data indicate that RBC-IC are able to stimulate the type of interactions between PMN and EC that are believed to cause EC damage and may play a role in the initiation or exacerbation of inflammatory vascular lesions.

Antigen-Antibody Complex↗
PubMed1987

Generation of phenotypically distinct macrophage-hepatoma hybrid clones.

By fusion of C3H/HeJ splenic adherent mononuclear cells enriched for macrophages with HPRT-deficient C57L/J HH- hepatoma cells, we have generated six macrophage-hepatoma hybrid clones. The hybrid nature of isolated clones was demonstrated by karyotypic analysis. The hybrid clones were screened for macrophage properties by assaying the presence of two enzymes: nonspecific esterase and lysozyme. Three of six hybrids expressed higher amount of Ia antigen and less amount of FcR; the other three hybrids expressed higher amounts of Fcr, but no Ia antigen. Phagocytosis of serum-opsonized beads is positively correlated with FcR expression, while the proliferation of antigen-primed lymphocytes is only induced by antigen-pulsed hybrids expressing Ia antigen. One hybrid clone (MH3-1) secreted significantly higher level of PGE2 and also expressed Ia antigen with higher ability of antigen-presentation. The data suggest that the cell hybridization can segregate macrophage-featured phenotypes into different hybrid clones which perform distinct functions. It may facilitate the study on the relationship of macrophage functions and the relationship between the functions and defined cell structure.

Animals↗
PubMed1987

Treatment of acute serum sickness by plasma ultrafiltration.

The clinical value of a scaled-down prototype of an extracorporeal plasma ultrafiltration system for the treatment of acute serum sickness in rabbits was examined. The system uses two filters: the primary separates red cells from plasma, and the secondary filter excludes high molecular weight proteins from plasma. In vitro and in vivo experiments showed that the secondary filters rejected substantially more IgM (80-90%) than IgG (10-30%) or albumin (10%) and totally rejected immune complexes (IC) prepared in vitro. Two groups of rabbits were submitted to either sham filtration with the primary filter only (n = 5), receiving back the remixed components of their blood, or to the complete ultrafiltration protocol (n = 7), with removal of high molecular weight proteins and IC. Several parameters were studied longitudinally, such as circulating IC, which appeared to rise more slowly in animals whose blood was ultrafiltered, and total proteinuria, which appeared to remain at lower levels in the same animals. Histologic examination of the kidneys, collected after killing, showed evidence of glomerular IC deposition in three of five sham-treated animals (a similar frequency to that observed in a separate group of five rabbits with acute serum sickness), while one of six treated animals had evidence of glomerular deposition of IC. These observations are tentative because of the small number of animals in each group, but are encouraging. Further studies with larger groups of animals are needed to determine whether the observed effects are reproducible and to better characterize the factors directly related to the removal of circulating IC.

Acute Disease↗
PubMed1987

Autologous red blood cells potentiate antibody synthesis by unfractionated human mononuclear cell cultures.

We have tried to determine the most favourable conditions for the in vitro induction of specific antibody (Ab) responses to tetanus toxoid (TT) and keyhole limpet haemocyanin (KLH). Human peripheral blood mononuclear cells (PBMNC) were obtained from normal volunteers and stimulated with PWM, TT, KLH, and mixtures of PWM and antigens in the presence or absence of autologous red blood cells (RBC) (1:50 ratio of PBMNC/RBC). The cultures were harvested on day 11; immunoglobulins were determined immunonephelometrically and Ab levels by ELISA with human antibodies used for calibration. While anti-TT responses were easy to induce with PBMNC from recently boosted individuals, the production of anti-TT from PBMNC obtained from non-recently boosted individuals was only possible when PBMNC were stimulated with TT and PWM in the presence of autologous RBC. Similarly, anti-KLH responses were easier to induce with PBMNC from an immune donor; maximal response was observed after stimulation with PWM + KLH in the presence of autologous RBC. Stimulation of primary anti-KLH responses with PBMNC from non-immune donors was only successful when the cells were stimulated with KLH + PWM in the presence of autologous RBC. The potentiation of human B-cell responses with autologous RBC can be abrogated by pretreatment of PBMNC with anti-CD2 antibodies and is associated with increased expression of IL-2 receptors and increased production of gamma interferon (IFN-gamma). However, addition of IFN-gamma in different doses and at different times to PWM-stimulated PBMNC cultures was not as effective as addition of RBC in enhancing the production of immunoglobulin and antibody.

Antibody Formation↗
PubMed1986

Immunoglobulin class of anti-Candida antibodies in patients with vaginal candidiasis.

Studies of the immunoglobulin class of circulating anti-Candida antibodies in patients with vaginal candidiasis were undertaken with the aim of answering the question of whether these antibodies are predominantly IgA or IgG. Earlier work resulted in conflicting data that we felt would be clarified by the use of a quantitative technique, FIAX fluoroimmunoassay, which could objectively measure the relative amounts of antibody of each class. Results using this assay and the indirect immunofluorescence assay on whole Candida cells demonstrate that the immunoglobulin class distribution of the circulating anti-Candida antibodies of these patients is similar to that seen in other forms of Candida infection, the predominant antibody class being IgG.

Antibodies, Fungal↗
PubMed1986

Apheresis, exchange, adsorption and filtration of plasma: four approaches to the removal of undesirable circulating substances.

Plasmapheresis and plasma exchange have been widely used in the treatment of a variety of conditions, not always with a clear rationale. The most favorable results have been observed in the hyperviscosity syndrome and in a group of antibody-mediated diseases which includes post-infectious cold agglutinin disease, red cell aplasia, post-transfusion purpura, Goodpasture's syndrome, hemophilic patients with anti-factor VIII antibodies, and also in thrombotic thrombocytopenic purpura. In contrast, disappointing or conflicting results have been obtained in immune complex diseases, myasthenia gravis, cryoglobulinemia, etc. It seems likely that at least some of the difficulties may arise from the non-specific removal of a variety of substances as well as for our lack of understanding of immunological feed-back mechanisms which are disturbed by plasmapheresis and related techniques. Future developments are likely to be centered in the development of more specific approaches as based on filtration, affinity chromatography and adsorption to antibodies or other substrates. These approaches appear promising for the removal of "blocking factors" in patients with cancer, lipoproteins in patients with hypercholesterolemia, immune complexes, and toxic compounds. A cautiously optimistic approach to such new developments and their testing in animal models and in carefully controlled patient trials are essential. The principles on which these therapeutic approaches lie are valid, and the skepticism that surrounds them may be underserved, since it was largely the result of an indiscriminate use of non-selective procedures.

Adsorption↗
PubMed1986

The binding of immune complexes to human red cells: complement requirements and fate of the RBC-bound IC after interaction with human phagocytic cells.

Soluble immune complexes (IC) are known to bind to human red blood cells (HRBC). Most authors have attributed this binding to the interaction between IC-bound C3b and a red cell CR1 receptor, but contradictory data has been published concerning the ability of IC to bind to HRBC in the absence of complement. Using soluble tetanus toxoid-rabbit anti-tetanus toxoid (TT-ATT) IC, we have shown that binding through the CR1 receptor takes place when IC are formed at antibody excess, while IC formed at antigen excess do not require complement for erythrocyte binding. Once absorbed to HRBC, IC are recognized by CR1 and/or Fc receptors on phagocytic cells. This interaction is not associated with red cell engulfment, but using radiolabelled S. aureus protein A as a probe, we have demonstrated the transfer of IC from HRBC to phagocytic cells. Such transfer without red blood cell (RBC) damage agrees with the postulated role of RBC in the elimination of soluble IC from circulation. However, we have also demonstrated that the interaction between HRBC-IC and phagocytic cells is associated with the release of mediators of inflammation. It is, therefore, not absolutely clear whether the interaction of RBC-adsorbed IC and phagocytic cells will always have beneficial consequences.

Antigen-Antibody Complex↗
PubMed1985

Evidence for the biclonal nature of a Waldenstrom's macroglobulinemia.

The serum of a patient with Waldenstrom's macroglobulinemia was shown to contain two IgM(kappa) paraproteins of different electrophoretic mobilities on cellulose acetate and immunoelectrophoresis and were designated IgM slow (s) and IgM fast (f). Both existed as high molecular weight polymers and contained a J chain. The two pentameric IgM monoclonal proteins were shown to be completely distinct in carbohydrate composition as determined by gas chromatography and periodic acid-Schiff staining, in molecular weight, by physicochemical properties, peptide mapping, amino-acid composition, NH2-terminal sequence, subgroup of light chains, and by lack of shared idiotypic determinants as determined by hemagglutination inhibition studies. Our study presents strong evidence for the 'bioclonal' nature of this gammopathy. We conclude that both paraproteins are distinct and originated from different B cells.

Amino Acid Sequence↗
PubMed1985

Erythrocyte-bound immune complexes trigger the release of interleukin-1 from human monocytes.

We have demonstrated herein that immune complexes (IC) bound to O+ human erythrocytes trigger the release of interleukin-1 (IL-1) from human monocytes in vitro. The efficiency of monocytes stimulation by erythrocyte-bound IC is in sharp contrast to the lack of stimulation of monocytes by soluble IC. The IL-1 activity triggered by erythrocyte-bound IC was lower than that induced by insoluble IC or opsonized fluorescent latex beads, but was greater than that induced by anti-D-treated O+ human erythrocytes. The magnitude of IL-1 release induced by insoluble IC and erythrocyte-bound IC were similar up to 18 hr of incubation. The IL-1 activity decreased in the supernatant of monocytes exposed to erythrocyte-bound IC for 40 hr, while the activity of IL-1 induced by insoluble IC remained at a high level. The physiological and physiopathological significance of triggering IL-1 release by erythrocyte-bound IC are discussed.

ABO Blood-Group System↗
PubMed1985

Immunological and microbiological factors in the pathogenesis of atherosclerosis.

Among the several pathological events that lead to the formation of an atheromatous lesion, endothelial cell damage, smooth muscle cell proliferation, and foam cell formation, are considered as particularly significant. In this review we summarize data suggesting that immunological and microbial factors may cause, directly or indirectly, these pathological events. Binding of immunocomplexes to endothelial cells, phagocytic cells, platelets, or erythrocytes could be the starting point for a variety of circuits leading to endothelial cell cytotoxicity and to the release of a variety of mediators, including cell proliferative factors. Endothelial cell toxicity could also be induced, directly or indirectly, by endotoxin; however, the possibility that endotoxin and other microbial factors may induce abnormalities in lipid metabolism at the monocyte/macrophage level which eventually result in intracellular accumulation of cholesterol (particularly if cholesterol levels are elevated) is specially attractive as a potential pathogenic mechanism. The various pathologic pathways discussed in this review appear plausible on the basis of our current knowledge and point to the need to investigate the potential role of infectious processes, autoimmune reactions, and administration of antigenic compounds as possible risk factors for the development of atherosclerosis.

Acetylmuramyl-Alanyl-Isoglutamine↗