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Biomedical subjects

A Tarkowski

Publications and source records attributed to A Tarkowski.

At least 109 records · Page 6Linked to original sources
PubMed1996

IL-10-driven immunoglobulin production by B lymphocytes from IgA-deficient individuals correlates to infection proneness.

In search for a possible explanation of the phenotypic heterogeneity in IgA deficiency, we studied the function of B cells from IgA-deficient (IgAd) individuals. Two groups of IgAd individuals, one frequently infected and one clinically apparently healthy, as well as normal controls, were studied. Peripheral blood mononuclear cells (PBMC) and B cells from IgAd individuals and controls were cultured with Staphylococcus aureus Cowan I strain and with anti-CD40 MoAb presented on the CD32-transfected fibroblast cell line in the presence of IL-10. In this experimental system PBMC and B cells from the infection-prone IgAd individuals produced only minute amounts of IgA. In contrast, PBMC and B cells from healthy IgAd subjects secreted significantly more IgA1 and IgA2 in comparison with infection-prone IgAd patients (P < 0.05). These data suggest that the abnormalities of B cell differentiation in IgAd could be of heterogeneous origin. Thus, whereas in healthy IgAd subjects IgA production may be efficiently up-regulated in vitro by addition of IL-10 to CD40-activated B cell culture, the corresponding B cell differentiation does not occur in infection-prone IgAd patients. These observations provide a conceptual framework for phenotypic heterogeneity in IgAd subjects.

Adult↗
PubMed1996

Catecholamines are synthesized by mouse lymphocytes and regulate function of these cells by induction of apoptosis.

The immune and the nervous systems are anatomically closely related and interact with each other by molecules common to both systems, such as cytokines and neurotransmitters. The purpose of this study was to investigate the participation of catecholamines in the neuroimmunological network. The ability of immune cells to produce catecholamines was examined by a highly sensitive capillary electrophoresis assay, which permits detection of easily oxidized catecholamines in the zeptomole (10(-21)) range. In addition, the effects of catecholamines on in vitro proliferation, differentiation and apoptosis of lymphocytes were assessed. Mouse spleen cells and macrophages contained on average 7 x 10(-17) and 2 x 10(-17) mole dopamine per cell, respectively. In the former cell population also norepinephrine was found. Several mouse B- and T-cell hybridomas were also shown to contain endogenously produced dopamine in levels ranging from 7 x 10(-20) to 2 x 10(-18) mole dopamine per cell. In addition, one of the T-cell hybridomas proved to synthesize norepinephrine. The dopamine production of lymphocytes was blocked by the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine, whereas incubation with the precursor L-DOPA increased the dopamine content. Incubation with L-DOPA, dopamine and norepinephrine dose-dependently suppressed mitogen induced proliferation and differentiation of mouse lymphocytes. Even short-time pretreatment of lymphocytes with L-DOPA and dopamine strongly suppressed lymphocyte proliferation and cytokine production. Incubation of lymphoid cells with L-DOPA, dopamine and norepinephrine dose-dependently induced apoptosis which, at least partly, explains the suppressive effects of catecholamines on lymphocyte function. Our results demonstrate that catecholamines: (i) are actively produced by lymphocytes and (ii) have the capacity to act as auto- and/or paracrine regulators of lymphocyte activity through induction of apoptosis.

Animals↗
PubMed1996

Limited T-cell receptor V gene usage in inclusion body myositis.

Inclusion body myositis (IBM) is a chronic, progressive inflammatory myopathy. The inflammatory infiltrates are dominated by T cells, which frequently invade muscle fibres. The present study was performed to characterize the usage of the variable (V) segment of the T-cell receptor of muscle infiltrating cells in IBM. Using the reverse transcriptase polymerase chain reaction (RT-PCR) technique the authors analysed the expression of 22 V alpha and 24 V beta families in muscle tissue from six patients with IBM displaying intense inflammatory cell infiltration. The following V alpha/V beta families appeared in at least 50% of the patients: V alpha 1, 5, 7, 15, 16, 17, 20, 21, 22 and V beta 3, 5.2, 8, 12, 14, 22. In all patients V alpha 7, 16 and V beta 8 were expressed in muscle tissue. Furthermore, in two of the patients peripheral blood lymphocytes (PBL) were investigated in parallel. There was a restricted usage of V alpha and V beta families in muscle in comparison to PBL, indicating a selective homing or local proliferation of T lymphocytes in the inflammatory lesions in IBM.

Adult↗
PubMed1996

Participation of V beta 4(+)-, V beta 7(+)-, and V beta 11(+)-T lymphocytes in haematogenously acquired Staphylococcus aureus nephritis.

The most frequent pathogen in haematogenously acquired kidney infections in humans in Staphylococcus aureus. In order to characterize in situ the immunological patterns of septic nephritis we developed a murine model of this disease. A single intravenous injection of S. aureus producing toxic shock syndrome toxin-1 resulted in high frequency of inflammatory kidney lesions. Histopathologically, both focal and diffuse inflammatory infiltrates were seen in kidney cortex and medulla. Immunohistochemical evaluation revealed high numbers of Mac-1+ phagocytic cells as well as CD4(+)-and CD8(+)-lymphocytes. The expansion of lymphocytes carrying T-cell receptor V beta chain 4, 7, and 11 families in the kidney was observed. Our results suggest that the haematogenously acquired kidney infection by superantigen-producing staphylococci leads to migration, in situ activation and expansion of responding T-lymphocyte subsets.

Animals↗
PubMed1996

Effects of cyclosporine A on plasma cells in experimental gingivitis in dogs.

The aim of the present investigation was to evaluate the effect of Cyclosporine A (CsA) on the inflammatory lesion formed in the gingival tissues during de novo plaque formation. 5 beagle dogs were used. On day 0, all teeth of the 5 dogs were scaled and polished. A 6-week period of plaque control including daily tooth cleaning with toothbrush and dentifrice was initiated. A clinical examination regarding plaque and gingivitis was performed, and the plaque control measures were abandoned on the right side of mandible. 3 weeks later, the clinical examination was repeated, samples of subgingival plaque harvested and biopsies obtained from the 3rd and 4th right mandibular premolar regions. The tooth cleaning measures on the left side of the mandible were terminated at this interval. During the following 3 weeks, the animals formed plaque in the lower left premolar regions, and received, 1 x daily, a subcutaneous injection of CsA. At the end of this 2nd plaque formation period (test), the clinical examination was repeated, subgingival plaque was sampled and biopsies from the 3rd and 4th left mandibular premolar regions harvested. The biopsies were prepared for histometric and morphometric analyses. The clinical and histological examinations demonstrated that plaque formation resulted in a gingival lesion (ICT) which, in the 2 periods, had similar size and apical extension. The ICT formed during the CsA administration period, however, harbored an increased number of plasma cells and a reduced macrophage density than the control lesion. It is suggested that CsA administration may result in a Th-2 (T-helper 2-cell) dependent activation of B-lymphocytes.

Aggregatibacter actinomycetemcomitans↗
PubMed1996

Vitamin A deficiency predisposes to Staphylococcus aureus infection.

We have investigated the consequences of vitamin A deficiency in a rat model of T-cell-dependent and superantigen-mediated Staphylococcus aureus arthritis. After intravenous inoculation of enterotoxin A-producing staphylococci, the vitamin-A-deficient rats showed a decreased weight gain compared with the paired fed controls despite equal food consumption. The control rats developed arthritis in the first few days after bacterial inoculation, with a peak frequency at day 5, and then gradually recovered; however, the frequency of arthritis 18 days after bacterial inoculation was 86% among the vitamin A-deficient rats and 44% among the control rats. During this period, 3 of 10 deficient rats and 1 of 10 control rats died. Further in vitro analysis revealed that T-cell responses to S. aureus were significantly higher in the vitamin A-deficient rats than in the control animals. In contrast, B-cell reactivity, measured as immunoglobulin levels, autoantibody levels, and specific antibacterial antibody levels in serum, did not differ between the groups. Interestingly, the innate host defense mechanisms against S. aureus were also profoundly affected by vitamin A deficiency. Thus, despite a larger number of circulating phagocytic cells in the vitamin-A-deficient group, the capacity to phagocytize and exert intracellular killing of S. aureus was significantly decreased in comparison with the control rats. Furthermore, serum from the vitamin A-deficient rats inoculated with Staphylococcus aureus displayed decreased complement lysis activity. Our results suggest that the increased susceptibility to S. aureus infection observed in the vitamin-A-deficient rats is due to a concerted action of antigen-specific T-cell hyperactivity, impaired function of the phagocytes, and decreased complement activity.

Adaptation, Biological↗
PubMed1996

Role of the staphylococcal accessory gene regulator (sar) in septic arthritis.

Staphylococcus aureus arthritis is a highly erosive disease in which both host and bacterial factors are of importance for its induction and progression. At the transcriptional level, three known loci act in regulating production of exoproteins and expression of cell wall structures. The aim of our study was to assess the role of the sar locus as a virulence determinant in the pathogenesis of septic arthritis. A recently established murine model of hematogenously spread S. aureus arthritis was employed. S. aureus strains, isogenic for the sar locus, were inoculated intravenously into NMRI mice, and the clinical, bacteriological, serological, and histopathological progression of the disease was studied. Within 1 week after inoculation of bacteria, the frequency of arthritis was 79% in the group of mice inoculated with the sar+ strain, whereas the corresponding frequency in sar mutants was 21% (P < 0.01). Mice inoculated with the sar+ staphylococcal strain exhibited a more pronounced T- and B-lymphocyte activation than those inoculated with the sar mutant, evidenced by splenomegaly, polyclonal B-cell activation, and high serum levels of interleukin 6 and gamma interferon. Also, infection with sar+ staphylococci induced a pronounced weight loss. To assess the relationship between clinical signs and spread of bacteria, we analyzed the homing pattern and persistence of S. aureus in host tissues. Kidneys and joints from sar+-inoculated subjects displayed a higher degree of bacterial persistence than other organs. Our results suggest that molecules controlled by the sar locus are important virulence determinants in the induction and progression of septic arthritis.

Animals↗
PubMed1996

Role of intercellular adhesion molecule 1 in pathogenesis of staphylococcal arthritis and in host defense against staphylococcal bacteremia.

Intercellular adhesion molecule 1 (ICAM-1) is a member of the immunoglobulin superfamily that interacts with two integrins, LFA-1 and Mac-1. These interactions are critical for leukocyte extravasation into inflamed tissue. To assess the role of ICAM-1 expression in the pathogenesis of bacterial infection, homozygously mutant mice lacking the ICAM-1 gene were exposed to Staphylococcus aureus. Within 6 days after inoculation 50% of the animals in the ICAM-1(-/-) group, but none of the controls, had died. Despite the high level of mortality, ICAM-1(-/-) mice developed less frequent and less severe arthritis than their wild-type littermates. In agreement, normal mice inoculated with staphylococci and administered anti-ICAM-1 antibodies exhibited a higher frequency of mortality but less severe arthritis than the controls. Our results indicate that ICAM-1 on the one hand provides protection against systemic disease but on the other hand aggravates the local disease manifestation.

Animals↗
PubMed1996

Increased release of tumor necrosis factor-alpha and interleukin-6 in women with the syndrome of hemolysis, elevated liver enzymes, and low platelet count.

BACKGROUND: Complement is activated in preeclampsia and complement products are known to activate macrophages. The aim of this study was to determine whether the macrophage derived cytokines, interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha, are released in patients with a form of severe preeclampsia characterized by the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome). METHODS: Complement activation and plasma levels of cytokines were studied in 11 women with HELLP syndrome and in 11 controls with uncomplicated pregnancies. To further evaluate the connection between complement activation and cytokine release an in vitro study on heparinized whole blood incubated with recombinant C5a was performed. RESULTS: In the HELLP group, complement anaphylatoxin C5a was increased in plasma at delivery (p < 0.01) and one day after delivery (p < 0.05), terminal C5b-9 complement complex was elevated in plasma at delivery (p < 0.001) and one day after (p < 0.01), plasma levels of interleukin-6 were increased one day after delivery (p < 0.01), and plasma concentrations of tumor necrosis factor-alpha were elevated at delivery (p < 0.01), compared with corresponding levels in controls. All parameters normalized within one week. Interleukin-I beta did not differ between the groups. In vitro, recombinant C5a incubated in whole blood gave a dose-dependent release of interleukin-6. No increased release of interleukin-1 or tumor necrosis factor-alpha was seen after incubation. CONCLUSIONS: Since cytokine release occurs in severe preeclampsia, inflammatory mechanisms may participate in the pathophysiology of severe preeclampsia.

Adult↗
PubMed1996

Intra-articular administration of polyclonal immunoglobulin G in rheumatoid arthritis. A double-blind, placebo-controlled pilot study.

The aim of our study was to assess local anti-inflammatory effects of high dose immunoglobulin G (IgG) in rheumatoid arthritis (RA). Eleven patients with definite RA, having flare-up of knee joint synovitis, were included in the study. Six received an intra-articular injection of 1 g of IgG in 10 ml saline and five received an intra-articular injection of 10 ml physiological saline alone. The effect of the treatment was evaluated clinically and by magnetic resonance imaging using gadolinium contrast enhancement. In one of the six patients that received intra-articular IgG and one of the five patients that received physiologic saline a modest decrease of synovial hypertrophy was noted. None of the patients experienced clinical signs of increased joint inflammation as a consequence of the treatment procedures. The results of this pilot, double-blind, placebo-controlled study do not support local administration of IgG as an anti-inflammatory treatment in patients with RA.

Arthritis, Rheumatoid↗
PubMed1996

Expression of the mucosal lymphocyte integrin alpha E beta 7 and its ligand E-cadherin in the synovium of patients with rheumatoid arthritis.

The synovial expression of the mucosal lymphocyte integrin alpha E beta 7 and its ligand E-cadherin was analysed in order to study the relationship between T lymphocytes of the gastrointestinal tract and the synovium in patients with rheumatoid arthritis (RA). Immunohistochemical evaluation of synovium revealed that the alpha E beta 7-expression was detectable in 16 of the 38 samples examined. A concomitant examination on circulating lymphocytes by flow cytometry showed that alpha E beta 7-expressing lymphocytes occur less frequently in peripheral blood (PB). In vitro culture of lymphocytes increased the alpha E beta 7-expression on synovial lymphocytes six-fold, whereas PB lymphocytes expressed a two-fold increase. The addition of PHA to the culture medium did not dramatically increase the alpha E beta 7-expression on synovial lymphocytes, in contrast to PB lymphocytes where a 24-fold increase was detected. The addition of TGF-beta 1 to the culture of PB lymphocytes increased the alpha E beta 7-expression three-fold. E-cadherin expression was found in all synovial tissues analysed by immunohistochemistry. These results demonstrate that synovial T lymphocytes have the capacity to express the 'mucosal-type' integrin alpha E beta 7, possibly due to high levels of intra-articular TGF-beta 1. This expression might be of physiological importance since E-cadherin, the ligand for alpha E beta 7, is richly expressed by synoviocytes. In addition, the results indicate that a high in vivo expression of alpha E beta 7 is suppressed in the synovial tissue by a hitherto unknown mechanism.

Adult↗
PubMed1995

Impact of interferon-gamma receptor deficiency on experimental Staphylococcus aureus septicemia and arthritis.

The role of IFN-gamma in the regulation of host resistance of Staphylococcus aureus was studied using IFN-gamma receptor-deficient (IFN-gamma R-/-) mice in a model of S. aureus-induced septicemia and arthritis. IFN-gamma R-/- mice and wild-type controls were inoculated intravenously with a toxic shock syndrome toxin-1-producing S. aureus LS-1 strain. IFN-gamma R-/- mice displayed significantly more frequent and more severe arthritis compared with wild-type littermates (p < 0.01) throughout the course of infection. Notably, IFN-gamma R-/- mice developed severe sepsis with high mortality early after the inoculation with staphylococci. However, the mortality of wild-type mice became significantly higher at later stages of the disease compared with IFN-gamma R-/- mice (p < 0.05). This differential outcome of sepsis-related mortality was associated with deficiencies of bacterial elimination from blood and parenchymatous organs and correlated well to serum levels of IL-6 and spleen IL-1 beta and TNF-beta mRNA expression. Thus, bacterial growth and proinflammatory cytokines IL-1 beta, TNF-beta, and IL-6 were higher at the early stage of infection in IFN-gamma-/- mice but increased at the later stage in wild-type littermates. Our data indicate that the absence of IFN-gamma R leads to harmful as well as beneficial effects in S. aureus infection, depending on the stage of the disease and the localization of the infection.

Animals↗
PubMed1995

Mice with the xid B cell defect are less susceptible to developing Staphylococcus aureus-induced arthritis.

To investigate the role of B cells in the development of experimental Staphylococcus aureus-induced arthritis, we used X-linked immunodeficiency (xid) mice that carry a Bruton's tyrosine kinase mutation affecting the function of B cells. NFR/N.xid and congenic NFR/N mice were inoculated i.v. with a toxic syndrome toxin-1 producing S. aureus LS-1 strain. B cell-deficient NFR/N.xid mice developed less frequent (p < 0.01) and less severe (p < 0.01) arthritis than NFR/N mice did. These clinical findings were corroborated by histopathologic evaluation, indicating that NFR/N.xid mice had significantly lower (p < 0.01) erosivity of the disease. Interestingly, infected NFR/N.xid mice showed decreased bacterial burden in blood, joints, and other organs compared with the control mice. Serologic studies displayed poor B cell responses to staphylococcal cell walls, toxic shock syndrome toxin-1, and ssDNA, accompanied by a low level of Igs in infected NFR/N.xid mice. More importantly, xid defect affected cytokine profile. The in vitro experiments showed that the lymphocytes from NFR/N.xid mice had low IL-6, but high IFN-gamma production upon stimulation with staphylococcal cell walls compared with NFR/N mice. Furthermore, the in situ hybridization technique revealed the relative increase of IFN-gamma, but marked decrease of IL-1 beta mRNA expression in spleens of infected NFR/N.xid mice. No significant difference in IL-4, IL-10, and TNF-alpha mRNA expression was found between both strains. Our findings demonstrate that B cells may, directly or indirectly, contribute to the pathogenesis of septic arthritis. The results indicate that increased IFN-gamma production along with low IL-6 and IL-1 beta synthesis found in xid mice may provide a more favorable outcome of S. aureus arthritis.

Animals↗
PubMed1995

Patterns of interferon-gamma mRNA expression in toxic shock syndrome toxin-1 expanded V beta 11+ T lymphocytes.

We have recently demonstrated that toxic shock syndrome toxin-1 (TSST-1), a staphylococcal exotoxin with superantigenic properties, is involved in the pathogenesis of septic arthritis. The aim of the current study was to characterize in detail the in vitro properties of TSST-1 with regard to T cell activation patterns. We demonstrate that TSST-1 preferentially expands murine V beta 11+ T lymphocytes and this expansion occurs equally well within CD4 and CD8 compartments. To analyze the functional properties of V beta 11+ T cells expanded in response to TSST-1, we have utilized a combined in situ hybridization and immunocytochemistry method. With this technique we show that TSST-1-stimulated V beta 11+ T cells are an important source of IFN gamma mRNA synthesis, suggesting that this cytokine may participate in superantigen-mediated septic arthritis.

Animals↗
PubMed1995

Local T-cell proliferation and differentiation in inflammatory myopathies.

Our objective was to investigate the patterns of proliferation and differentiation of infiltrating cells in inflammatory myopathies. Immunohistochemical staining was performed on muscle biopsy specimens from 18 patients with inclusion body myositis, polymyositis and dermatomyositis using monoclonal and polyclonal antibodies. An abundance of cells were TNF-alpha+ (4-8%), ICAM-1+ (7-65%), IFN-gamma+ (3-6%), and Ki-67+ (4-8%). It was shown that 70% of the Ki-67+ cells were Ki-67+CD3+ cells. Very few mononuclear cells were IL-2R+. MHC-I expression was found on nearly all muscle fibres in all cases, while MHC-II expression was found on occasional muscle fibres in 1/3 of cases. Analysis of repeated biopsies from four IBM patients after prednisolone treatment showed no change in the proportions of TNF-alpha, ICAM-1, IFN-gamma or Ki-67 positive cells. In inflammatory myopathies there is an intense proliferation and differentiation of inflammatory cells in situ, indicating a local stimulation of the inflammatory process.

Adult↗