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At least 829 records · Page 46Linked to original sources
PubMed1983

In vitro hematoporphyrin (Hpd) inhibitory effects on some immunological assays.

Hematoporphyrin derivative (Hpd) is a fluorescent dye that is preferentially incorporated by tissues with a high mitotic index, such as tumor cells and blast cells. A cytotoxic effect is produced following light activation. Previous studies have shown a long lasting reversible inhibition of DNA synthesis in Hpd-treated cells that failed to stimulate allogeneic lymphocytes in either primary or in secondary MLR. In this study we report Hpd inhibitory effects on some immunological assays in vitro. Treatment with Hpd of cytotoxic effector cells resulted in inhibition of their lytic activity likely dependent on the loss of binding to target cells. In the same way Hpd treatment inactivated the lytic activity of NK cells. In contrast Hpd-treatment of target cells did not modify the above immunological reactions. Moreover Con A agglutinability, antibody dependent capping as well as E-rosettes were inhibited following an Hpd treatment of relevant cells. Since normal susceptibility to humoral and cell mediated lysis was exhibited by Hpd-treated cells it is unlikely that cell surface molecules were damaged. An inhibitory effect exerted by an Hpd treatment on cell surface movements might explain these findings.

Agglutination↗
PubMed1979

Abnormal lymphocyte capping in a patient with severe combined immunodeficiency disease.

Despite the presence of normal numbers and distribution of T and B lymphocutes and normal levels of serum immunoglobulins, a five-month-old infant failed to show any evidence of T-cell or B-cell immunity. In trying to identify a specific membrane abnormality as a potential cause of the immunologic dysfunction, we examined the lateral mobility of the cell-surface receptor for concanavalin A. In contrast to normal cells, in which the receptor is distributed uniformly over the cell surface, the patient's lymphocytes showed an unusually high accumulation of concanavalin A receptors in surface caps. This capping abnormality appeared in both T and B lymphocytes and was exaggerated by colchicine, an inhibitor of microtubule assembly. These findings support the theory that plasma-membrane-cytoskeleton interactions have a role in the expression of specific immunity; the findings also identify new areas that should be considered in trying to understand the primary immunodeficiency diseases.

B-Lymphocytes↗
PubMed1995

Influence of aging and neurodegenerative disease on changes in band 3-like proteins in white blood cells.

Fluorescent microspheres were used to measure antibody-induced capping of leukocyte membrane proteins that are immunologically related to band 3, the anion exchanger of the erythrocyte. The degree of capping was found to increase with donor age. Surface labeling and capping characteristics of cells from healthy, age-matched controls were not different from those from patients with Alzheimer's disease, multi-infarct dementia, and Down's syndrome. Immunoblots, however, indicated increased expression and/or breakdown of band 3-like proteins in leukocytes from patients when compared with young and old control donors. These findings emphasize the possible involvement of band 3-like proteins of nucleated cells in aging and disease.

Adult↗
PubMed2004

Actin cytoskeleton regulates calcium dynamics and NFAT nuclear duration.

T-cell activation by antigen-presenting cells is accompanied by actin polymerization, T-cell receptor (TCR) capping, and formation of the immunological synapse. However, whether actin-dependent events are required for T-cell function is poorly understood. Herein, we provide evidence for an unexpected negative regulatory role of the actin cytoskeleton on TCR-induced cytokine production. Disruption of actin polymerization resulted in prolonged intracellular calcium elevation in response to anti-CD3, thapsigargin, or phorbol myristate acetate plus ionomycin, leading to persistent NFAT (nuclear factor of activated T cells) nuclear duration. These events were dominant, as the net effect of actin blockade was augmented interleukin 2 promoter activity. Increased surface expression of the plasma membrane Ca(2+) ATPase was observed upon stimulation, which was inhibited by cytochalasin D, suggesting that actin polymerization contributes to calcium export. Our results imply a novel role for the actin cytoskeleton in modulating the duration of Ca(2+)-NFAT signaling and indicate that actin dynamics regulate features of T-cell activation downstream of receptor clustering.

Actins↗
PubMed2002

CD28 plays a critical role in the segregation of PKC theta within the immunologic synapse.

The signaling pathways that lead to the localization of cellular protein to the area of interaction between T cell and antigen-presenting cell and the mechanism by which these molecules are further sorted to the peripheral supramolecular activation cluster or central supramolecular activation cluster regions of the immunologic synapse are poorly understood. In this study, we investigated the functional involvement of CD28 costimulation in the T cell receptor (TCR)-mediated immunologic synapse formation with respect to protein kinase C (PKC)theta; localization. We showed that CD3 crosslinking alone was sufficient to induce PKC theta; capping in naive CD4(+) T cells. Studies with pharmacologic inhibitors and knockout mice showed that the TCR-derived signaling that drives PKC theta; membrane translocation requires the Src family kinase, Lck, but not Fyn. In addition, a time course study of the persistence of T cell molecules to the immunologic synapse indicated that PKC theta;, unlike TCR, persisted in the synapse for at least 4 h, a time that is sufficient for commitment of a T cell to cell division. Finally, by using TCR-transgenic T cells from either wild-type or CD28-deficient mice, we showed that CD28 expression was required for the formation of the mature immunologic synapse, because antigen stimulation of CD28(-) T cells led to a diffuse pattern of localization of PKC theta; and lymphocyte function-associated antigen-1 in the immunologic synapse, in contrast to the central supramolecular activation cluster localization of PKC theta; in CD28(+) T cells.

Animals↗
PubMed1987

Both conserved signals on mammalian histone pre-mRNAs associate with small nuclear ribonucleoproteins during 3' end formation in vitro.

Pre-mRNA substrates containing sequences from human and mouse histone genes are accurately processed in a HeLa cell nuclear extract to generate mature 3' termini. When in vitro processing reactions containing either human histone H3 or mouse histone H3 transcripts are treated with RNase T1 and probed with antibodies specific for the Sm protein determinants or for the trimethylguanosine cap structure unique to the U RNAs present in small nuclear ribonucleoproteins, RNA fragments that encompass the site of 3' end formation on the pre-mRNA transcript are selectively recovered. Several different interactions are detected: at time zero, the protected region contains the upstream conserved hairpin loop structure; at later times during the reaction, protection extends beyond the site of 3' end formation to include the downstream conserved sequence element and the 5' cap of the transcript is bound as well. Possible interactions between Sm small nuclear ribonucleoproteins and these conserved sequence elements in histone pre-mRNAs are discussed.

Autoantigens↗
PubMed1996

Identification and characterization of the cytoplasmic antiproteinase (CAP) in human platelets. Evidence for the interaction of CAP with endogenous platelet proteins.

To define the presence and potential role of platelet-associated protease inhibitors, we initiated a study designed to characterize the platelet components that are responsible for the formation of two SDS-stable complexes of approximately 58 and 70 kDa initially observed following the incubation of 125I-thrombin and human platelets. We demonstrate that thermal-mediated unfolding of the 58-kDa complex between 125I-thrombin and a nonsecreted platelet protein leads to an apparent molecular mass of 70 kDa. This platelet component is functionally and immunologically indistinguishable from the cytoplasmic antiproteinase (CAP), also known as placental thrombin inhibitor, a recently cloned member of the ovalbumin family of intracellular serpins (serine proteinase inhibitors). CAP-specific mRNA and antigen were detected in human platelets, suggesting that CAP synthesis occurs concurrent with platelet development. Utilizing quantitative immunoblotting, CAP antigen was estimated at 1.014 +/- 0.181 microg/10(9) nonstimulated platelets. After platelet activation with the calcium ionophore A23187, CAP antigen was detected in released microparticles at approximately 0. 195 +/- 0.031 microg/10(9) platelets and a fraction of platelet CAP was proteolytically modified. We provide evidence that these lower molecular mass species arise by cleavage of CAP at or near the reactive site loop. Most importantly, molecular sieving chromatography indicates the presence of an approximately 68-kDa SDS-labile complex between cleaved CAP and a cellular component in A23187-stimulated platelets, suggesting a physiological target of this intracellular serpin and a potential role for this inhibitor in regulating proteolytic activity that may be formed during platelet activation.

Base Sequence↗
PubMed2006

Mortality in the catastrophic antiphospholipid syndrome: causes of death and prognostic factors in a series of 250 patients.

OBJECTIVE: To assess the main causes of death and the prognostic factors that influence mortality in patients with the catastrophic antiphospholipid syndrome (CAPS). METHODS: We analyzed the case reports of 250 patients included in the CAPS Registry up to February 2005. To identify prognostic factors for CAPS, we compared the main clinical and immunologic features and the types of treatment in the patients who died with those features in the patients who survived. RESULTS: Recovery occurred in 56% of the episodes of CAPS and death occurred in 44%. Cerebral involvement, consisting mainly of stroke, cerebral hemorrhage, and encephalopathy, was considered the main cause of death, being present in 27.2% of patients, followed by cardiac involvement (19.8%) and infection (19.8%). The only factor we identified that was prognostic of a higher mortality rate was the presence of systemic lupus erythematosus (SLE). A higher recovery rate was associated with combined treatment with anticoagulants (ACs) plus corticosteroids (CS) plus plasma exchange (PE) (77.8%), followed by ACs plus CS plus PE and/or intravenous immunoglobulins (69%). In contrast, concomitant treatment with cyclophosphamide did not demonstrate additional benefit. CONCLUSION: Cerebral involvement (mainly consisting of stroke), cardiac involvement, and infections were considered the main causes of death in patients with CAPS. The presence of SLE was related to a higher mortality rate. According to the results of the present study, ACs plus CS plus PE should be the first line of therapy in patients with CAPS.

Adult↗
PubMed1978

Different suppressive effects of combined cyclophosphamide-antigen treatment compared with exclusive cyclophosphamide treatment on primary and secondary humoral immune reactivity.

The immunosuppressive effect of a combined treatment with antigen (C3H erythrocytes - ME) and cyclophosphamide (CY - dosage 65% LD50) has been studied in inbred CAP rats showing different degrees of immunological reactivity. When primary reactivity existed before treatment, this reactivity was not abolished but diminished. When weak secondary reactivity (after one antigen injection) existed before treatment this reactivity was abolished and again diminished primary reactivity was found. When strong secondary reactivity (after 4 antigen injections) existed before treatment selective unresponsiveness was found during the 4 weeks following treatment. 12 weeks after treatment diminished primary reactivity was found again. When the same dose of CY was given without antigen no immunosuppressive effect could be seen - irrespective of whether primary, weak or strong secondary reactivity existed. The results indicate that in this model it is easier to induce selective unresponsiveness in sensitized than in nonsensitized rats and suggest that primed lymphocytes are more susceptible to a combined antigen-CY treatment than unprimed cells.

Animals↗
PubMed1984

Interaction of an acute phase reactant, alpha 1-acid glycoprotein (orosomucoid), with the lymphoid cell surface: a model for non-specific immune suppression.

alpha 1-Acid glycoprotein (AG), a serum component elevated during acute inflammation, has been implicated in the suppression of various immunological responses. Pretreatment of lymphoid cells with AG at a concentration commonly found in patients with acute inflammation results in the inhibition of mitogen induced lymphoproliferation as well as capping of concanavalin A (Con A) receptors and surface immunoglobulin (sIg) on the lymphoid cell surface. In order to determine a potential interaction of AG with the lipid bilayer we examined the effects of purified AG on synthetic phosphatidyl choline vesicles. AG displaces 1-anilino-8-naphthalene sulphonate (ANS), an anionic surface probe from these vesicles yet is unable to perturb the binding of N-phenyl-1-naphthalamine (NPN), a hydrophobic probe of the membrane interior. The non-immunosuppressive asialo-derivative of AG is incapable of displacing ANS from the vesicles. The interaction of AG with the membrane may partially involve electrostatic forces mediated by sialic acid and/or steric hindrance of receptor mobility. The results suggest that AG has the capacity to perturb the lymphoid cell surface and interfere with events required for lymphocyte proliferation.

1-Naphthylamine↗
PubMed1985

Ultrastructural change of the thymocyte surface after treatment with specific antibodies. A rapid-freezing and deep-etching study.

A specific surface change of mouse thymocytes induced by treatment with anti-Thy-1 antibody was ultrastructurally demonstrated by a rapid-freezing and deep-etching technique. Round elevations, 30 nm in diameter, were found on the exoplasmic surface (ES) face of the cell membrane of BALB/c mouse thymocytes (expressing Thy-1.2 on the cell surface) after treatment with non-labelled monoclonal anti-Thy-1.2 antibody, whereas the ES face without the treatment gave a smooth appearance. Immunological studies indicated that the elevation was induced by the specific antigen-antibody reaction. Further, the elevation was demonstrated to be located at the site of antigen-antibody reaction by the results of the protein A-gold test. It was also supported by the fact that the elevations showed cluster formations under capping conditions. Accordingly, the elevations were assumed to be antibody molecules or antigen-antibody complexes.

Animals↗
PubMed1978

Immunological characterization of a major transformation-sensitive fibroblast cell surface glycoprotein. Localization, redistribution, and role in cell shape.

The major cell surface glycoprotein of chick embryo fibroblasts, cellular fibronectin (formerly known as CSP or LETS protein), was purified and used to produce monospecific antisera. After affinity purification, the anti-fibronectin was used to investigate fibronectin's localization, its transfer from intracellular to extracellular pools, its antibody-induced redistribution on the cell surface, and its role in cell shape. Anti-fibronectin localizes to extracellular fibrils located under and between sparse cells, and to a dense matrix that surrounds confluent cells. Cellular fibronectin is also present in granular intracytoplasmic structures containing newly synthesized fibronectin before secretion. This intracellular staining disappears 2 h after treatment with cycloheximide or puromycin, and returns after removal of these protein synthesis inhibitors. In pulse-chase experiments using cycloheximide, fibronectin was sequentially transferred from the intracellular to the fibrillar extracellular forms. Transformation of chick fibroblasts results in decreases in both extracellular and intracellular fibronectin, and in altered cell shape. Treatment of untransformed chick fibroblasts with anti-fibronectin results in rapid (30 min) alteration to a rounder cell shape resembling that of many transformed cells. These rapid shape changes are followed by a slow, antibody-induced redistribution of fibronectin to supranuclear caplike structures. This "capping" is inhibited by metabolic inhibitors. Reconstitution of cell surface fibronectin onto transformed cells restores a more normal fibroblastic phenotype. The reconstituted fibronectin on these cells organizes into fibrillar patterns similar to those of untransformed cells. As with untransformed cells, treatment of these reconstituted cells with anti-fibronectin also results in cell rounding and "capping" of fibronectin.

Animals↗
PubMed2005

An indium:calcium phosphate colloid that specifically targets fibrin.

The ability of indium to target fibrin in vitro was evaluated. The radionuclide (114m)Indium (114mIn) was prepared as a soluble and colloidal (In:In) form, as well as, a mixed indium:calcium phosphate (In:CaP) colloid. Soluble 114mIn was prepared by maintaining acid pH (50 mM HCl). Colloidal 114mIn (In:In) was prepared under slightly basic conditions (50 mM Tris-Cl, pH 7.6). The mixed In:CaP colloid was prepared by incubation of 114mIn with calcium (10 mM) and phosphate (250 microM) under slightly basic conditions (50 mM Tris-Cl, pH 7.6). To assess fibrin binding, the three 114mIn preparations were mixed with diluted human plasma (source of fibrinogen). Fibrin polymerization was initiated by addition of calcium (5 mM) and thrombin (0.5 U/ml). Following incubation (15 min, 37 degrees C), the fibrin matrix was condensed, removed from the reaction mixture, and washed briefly. Fibrin uptake of 114mIn (soluble, colloidal, or In:CaP) was determined by gamma counting. Results demonstrated that soluble 114mIn exclusively bound a plasma protein electrophoretically and immunologically identified as transferrin. Although both colloidal 114mIn and 114mIn:CaP bound fibrin, the mixed 114mIn:CaP colloid demonstrated substantially higher fibrin binding activity (about 2-fold). The target of indium binding was confirmed as fibrin due to the presence of characteristic cross-linked gamma-gamma dimers (100 kDa) and beta-monomers (58 kDa) by SDS-PAGE. 114mIn colloid and the mixed 114mIn:CaP colloid demonstrated no ability to bind fibrin's precursor, fibrinogen. 114mIn:CaP fibrin binding was associated with formation of CaP, as evidenced by its dependence on phosphate concentration. The biocompatibility of CaP including its ability to bind 114mIn and specifically target fibrin may be of potential value for diagnostic imaging studies to identify regions of occult vascular stenosis (i.e., atherosclerotic plaques, deep vein thrombosis, pulmonary embolus).

Biocompatible Materials↗
PubMed1981

Immunological subsets in human B-cell lymphomas.

Fifty human B-cell lymphomas have been studied with regard to surface markers (surface immunoglobulins (sIg) and complement receptors (CR)), capping of sIg, and relative amounts of sIg by single-cell flow cytometry. The results show that these lymphomas can be subdivided into distinct immunological subsets. Whereas one histological subgroup (lymphocytic) consisted of only one immunological subtype, others were heterogeneous with regard to immunological subtypes. This was most striking in nodular lymphomas of germinal centre cell origin (centroblastic/centrocytic). Our studies provide further evidence for the existence of a large number of subsets in the B-cell compartment of the immune system, sIgD was only found in association with sIgM. The relative amounts of sIgD varied, especially in nodular lymphomas. A discrepancy between capping of sIgM and sIgD was also found in some lymphomas belonging to this group. These findings together with other observations suggest that sIgD plays a role in B-cell maturation and differentiation events taking place in germinal centres and becomes lost during this process. A close association was found between the presence of CR and capping of sIgM but not capping of sIgD or sIgG. Nodular lymphomas expressing sIgG only, lacked CR. These findings suggest that CR may become lost during maturation and differentiation processes also taking place in germinal centres. Lymphoplasmacytoid lymphomas, which show morphological evidence of differentiation towards plasma cells, could be subdivided into three immunological subsets, indicating that plasma cell maturation may take place from different subsets of B cells.

B-Lymphocytes↗
PubMed2003

Linking the T cell surface protein CD2 to the actin-capping protein CAPZ via CMS and CIN85.

Recruitment of CD2 to the immunological synapse in response to antigen is dependent on its proline-rich cytoplasmic tail. A peptide from this region (CD2:322-339) isolated CMS (human CD2AP); a related protein, CIN85; and the actin capping protein, CAPZ from a T cell line. In BIAcore analyses, the N-terminal SH3 domains of CMS and CIN85 bound CD2:322-339 with similar dissociation constants (KD = approximately 100 microm). CAPZ bound the C-terminal half of CMS and CIN85. Direct binding between CMS/CIN85 and CAPZ provides a link with the actin cytoskeleton. Overexpression of a fragment from the C-terminal half or the N-terminal SH3 domain of CD2AP in a mouse T cell hybridoma resulted in enhanced interleukin-2 production and reduced T cell receptor down-modulation in response to antigen. These adaptor proteins are important in T cell signaling consistent with a role for CD2 in regulating pathways initiated by CMS/CIN85 and CAPZ.

Adaptor Proteins, Signal Transducing↗
PubMed1986

In vitro effects of halothane on lymphocytes.

Many reports indicate that anaesthesia affects several immunological functions that decrease the immune response, but the mechanisms involved are still unknown. We investigated the in vitro effect of halothane on human lymphocyte metabolism and plasma membrane function by evaluating the intracellular concentration of 3',5'-cyclic adenosine-monophosphate (cAMP), phosphodiesterase enzyme activity, NAD+/NADH intralymphocytic ratios and the degree of antibody and lectine-induced 'capping' of surface markers. Our results demonstrated an impaired lymphocyte capping of surface immunoglobulins and concanavalin A receptors 60 min after exposure to halothane at the concentration of 1% in oxygen. This phenomenon was reversible after 24 h and it was unrelated to the presence of adherent cells during the culture. Furthermore, halothane was able to induce a persistent increase in cAMP intracellular concentrations, which was reversible within 48 h. This effect was not dependent on adherent cells or on phosphodiesterase enzyme inhibition. Finally, no alteration in NAD+/NADH ratios after halothane exposure was observed.

Cyclic AMP↗
PubMed2004

Integrative analysis of cancer-related data using CAP.

The development of human cancer is a highly complex process and can be considered the result of several combined events, such as genetic alterations, disturbance of signal transduction, or failure of immunological surveillance. Cancer-related databases usually focus on specific fields of research, e.g., cancer genetics or cancer immunology, whereas the complexity of cancer genesis requires an integrated analysis of heterogeneous data from several sources. Here we present the cancer-associated protein database (CAP), a novel analysis system for cancer-related data. CAP integrates data from multiple external databases, augments these data with functional annotations, and offers tools for statistical analysis of these data. We have employed CAP to analyze genes that have been found to cause an autoimmune response in cancer. In particular, we explored the connection between the autoimmune response, mutations, and overexpression of these genes. Our preliminary results suggest that mutations are not significant contributors to raising an antibody response against tumor antigens, whereas overexpression seems to play a more important role. We hereby demonstrate how different types of data can be integrated and analyzed successfully, providing interesting results. As the amount of available data is growing rapidly, a combined analysis will play an important role in exploring the genetic and immunological basis of cancer. CAP is freely available at the following web site: http://www.bioinf.uni-sb.de/CAP/.

Autoimmunity↗