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U Feige

Publications and source records attributed to U Feige.

At least 37 records · Page 2Linked to original sources
PubMed1992

Heat shock proteins in autoimmune disease. From causative antigen to specific therapy?

Heat shock proteins (hsp) are highly conserved from bacteria to man. Bacterial hsp, with approximate molecular weights of 60 kDa (hsp60), are immunodominant antigens that are immunologically cross-reactive with their mammalian counterparts. Hsp molecules are therefore useful in studies of fundamental questions concerning immune responses to foreign as opposed to self antigens. The finding that immune responses to hsp are associated with both experimentally-induced and spontaneous autoimmune diseases in animals has prompted intensive research to assess the role of bacterial hsp as the etiological agents involved in the development of autoimmune diseases. Recent evidence from animal models of autoimmune disease has clearly demonstrated the involvement of hsp in both the pathogenesis and the immunoregulation of autoimmune diseases. Studies with arthritogenic and diabetogenic T cell clones have identified immunogenic epitopes of hsp. These have been shown to ameliorate adjuvant arthritis in Lewis rats, and insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice. Such studies may have important therapeutic implications for the future treatment of human autoimmune disease.

Animals↗
PubMed1992

Prevention of adjuvant arthritis in rats by a nonapeptide from the 65-kD mycobacterial heat shock protein: specificity and mechanism.

In a previous study we have shown that Lewis rats were completely protected from adjuvant arthritis by pretreatment with a nonapeptide (residues 180-188) of the 65-kD mycobacterial heat shock protein. Here we address questions of specificity and mechanism(s) of protection. We demonstrate that complete protection against adjuvant arthritis can only be achieved by pre-immunization with the nonapeptide, while pretreatment with either the octapeptide (residues 181-188) of the 65-kD heat shock protein or unrelated immunogenic peptides failed to affect adjuvant arthritis. Interestingly, pretreatment with the nonapeptide of the 65-kD heat shock protein did not protect Lewis rats from type II collagen-induced arthritis. These results demonstrate that protection is both epitope and disease specific. Co-injection of the nonapeptide with mycobacterial antigen even at a weight ratio of 5:1 (nonapeptide:mycobacteria) failed to influence the disease, suggesting that the role of the nonapeptide is not as a 'blocking peptide'. T cells from rats immunized with nonapeptide respond to the nonapeptide as well as to mycobacteria in vitro, and adoptively transfer protection to naive recipients. The data indicate that the nonapeptide-induced protection may result from a T cell-mediated specific suppression.

Amino Acid Sequence↗
PubMed1990

Treatment of adjuvant arthritis in rats: vaccination potential of a synthetic nonapeptide from the 65 kDa heat shock protein of mycobacteria.

Adjuvant arthritis induced by mycobacteria in rats is a widely used model of chronic arthritis. A previously described nonapeptide (Thr-Phe-Gly-Leu-Gln-Leu-Glu-Leu-Thr, amino acid sequence 180-188) from the recombinant 65 kDa heat shock protein of Mycobacterium bovis BCG, which was found to contain a T-cell epitope recognized by both arthritogenic and protective T-cell clones in vitro, has been investigated for its vaccination and therapeutic potential in adjuvant arthritis in rats. The nonapeptide was found not to be arthritogenic, although the T cells from nonapeptide immunized rats cross-react in vitro with mycobacterial antigens. Intraperitoneal administration of 0.1 mg nonapeptide in oil at day -20 or days -2, -1 and 0, resulted in a marked reduction of incidence and severity of adjuvant arthritis. The disease process and severity were also influenced by therapeutic treatment with 0.1 mg nonapeptide injected intraperitoneally at days 7 to 10. Interestingly, subplantar or intravenous application of the nonapeptide had no influence on the disease process. Deletion of the N-terminal threonine led to complete loss of in vivo activity of the nonapeptide.

Amino Acid Sequence↗
PubMed1990

Prevention of adjuvant arthritis in rats by a nonapeptide from the 65-kD mycobacterial heat-shock protein.

Adjuvant arthritis in Lewis rats is a model of T cell-mediated autoimmune arthritis resembling human rheumatoid arthritis. A nonapeptide from the 65-kD heat-shock protein of Mycobacterium bovis BCG, amino acid sequence 180-188, has been described to carry the dominant immunogenic epitope(s) for both arthritis-protective and arthritogenic T cell clones. Here we demonstrate that immunizations with the synthetic nonapeptide completely protected rats against adjuvant arthritis induced by M. tuberculosis. Interestingly, deletion of the N-terminal threonine of the nonapeptide resulted in loss of the protective activity. Pretreatments with the nonapeptide resulted in an immune response to the nonapeptide and to M. tuberculosis. After immunizations with the synthetic nonapeptide, only low titres of nonapeptide-specific antibodies were produced, whereas a significant cellular immune response to the nonapeptide was observed. In addition, the protection was transferable to naive rats by spleen T cells. These findings document the requirement of a T cell-specific immune response to the dominant epitope of the 65-kD mycobacterial heat-shock protein for the protection against adjuvant arthritis and suggest the feasibility of immune intervention in autoimmune arthritis through the use of synthetic peptides.

Amino Acid Sequence↗
PubMed1990

Interactions of micromolar concentrations of fluoride with Streptococcus rattus FA-1.

Inhibition of the metabolic activities of bacteria by trace amounts of fluoride is manifested phenomenologically as changes in the pH gradient and/or the electrical potential between the cellular interior and the surrounding medium. These data were obtained from the intracellular/extracellular distribution of radioactivity labelled fluoride (18F), 5,5-dimethyloxazolidine-2,4-dione (14C), and tetraphenylphosphonium chloride (14C). When taken up from acidic media, trace concentrations of fluoride (1-100 microM) reduce the intracellular/extracellular pH gradient and affect the electrical potential across the cell membrane. The chromatographic fractionation of fluoride-charged bacterial homogenates showed that fluoride is attached to many proteins of the cytoplasm, the cell membrane, and to nonproteinaceous components of the cell wall. Lysozyme treatment synergistically affects the vulnerability of the bacteria to micromolar concentrations of fluoride.

Bacterial Proteins↗
PubMed1989

Differential immunological response of patients with rheumatoid arthritis towards two different Epstein-Barr virus strains: inhibition of interleukin-1 release by the B95-8, but not the P3HR-1 virus strain.

An abnormal immune response towards the Epstein-Barr virus (EBV) has been documented in patients with rheumatoid arthritis (RA). To investigate whether these findings are due to the transformation event caused by EBV, RA blood mononuclear cells and monocyte-enriched preparations were incubated with two different EBV strains: the transforming virus secreted by the cell line B95-8 and the virus released by the P3HR-1 cell line that is not able to transform due to a small deletion in the U2 region of the virus genome. Immunological response was determined by the production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) using ELISA and bioassay systems. There was a striking difference in cytokine measurements with a strong inhibition of IL-1 and TNF production after incubation with the B95-8 virus, but not the P3HR-1 virus. These data indicate that the disturbed reaction of the immune system towards EBV is either dependent on the full transformation of B cells in RA patients or alternatively due to the secretion of a cytokine inhibitor by the B95-8 cell line.

Arthritis, Rheumatoid↗
PubMed1989

An assay for the detection of interleukin-1 synthesis inhibitors: effects of antirheumatic drugs.

The monokines interleukin-1 beta and alpha (IL-1) play a central role in the connective tissue destruction of many chronic inflammatory diseases. A high capacity screening assay for the detection of inhibitors of IL-1 biosynthesis has been established. Normal human monocytes were obtained by leukapheresis and elutriation. IL-1 beta and alpha biosynthesis was stimulated with LPS, and cell-associated and secreted IL-1 beta and IL-1 alpha were measured by specific immunoassays (ELISA). The mean total IL-1 beta (cell-associated and secreted) production in 18 different donors was 11 ng/10(6) cells (range 1.2-28.8). Secreted IL-1 beta represented 31 to 86% of the total IL-1 beta. More IL-1 alpha than IL-1 beta was produced but, unlike IL-1 beta, IL-1 alpha was poorly secreted. The steroids prednisolone and dexamethasone, gold (sodium aurothiomalate) and chloroquine were potent inhibitors of the IL-1 production. Mean IC50 values of 180 nM (range 2.5 nM-1 microns), 10 microM (range 6-20 microM) and of 75 microM were found for prednisolone, gold and chloroquine, respectively. Above 5 microM, the non-steroidal anti-inflammatory compounds indomethacin and BW755C increased IL-1 beta biosynthesis. Nordihydroguaiaretic acid inhibited the level of the secreted form of IL-1 beta, but tended to increase the cell-associated level. D-Penicillamine (up to 6 mM), cyclosporin A (up to 1 microM) and methotrexate (up to 12 microM) inhibited neither cell-associated nor secreted IL-1 beta levels. This high capacity assay, which is insensitive to classical NSAIDs, may serve in the detection and characterization of new classes of anti-inflammatory compounds.

Anti-Inflammatory Agents↗
PubMed1989

Arthritis induced by continuous infusion of hr-interleukin-1 alpha into the rabbit knee-joint.

Continuous infusion of 200 ng/day hrIL-1 alpha for 14 days into knee-joints of rabbits leads to a severe arthritis of low aggressivity. This arthritis shows simultaneously characteristics of acute (serous and fibrinous exudation, polymorph infiltration, etc.) as well as chronic (synovial cell proliferation and fibrosis, pannus formation, cartilage and bone erosion, etc.) inflammation. The arthritis was associated with a distinct loss of metachromasia of the articular cartilage. These results indicate that IL-1 might play an important role in the induction and maintenance of arthritis.

Animals↗
PubMed1988

Interleukin-1 enhances pain reflexes. Mediation through increased prostaglandin E2 levels.

Interleukin-1 (IL-1) has been shown to induce inflammatory reactions in part through increased prostaglandin production. Prostaglandins of the E- and I-type sensitize nociceptors in peripheral tissues. We have therefore investigated the effect of IL-1 perfusion in the isolated rabbit ear, a model which allows the assessment of peripheral pain. Natural IL-1 from human monocytes, IL-1 from glioblastoma cells as well as recombinant IL-1 alpha or beta, increased the pain reflex induced by acetylcholine in a concentration dependent manner. The PGE2 levels were measured in the perfusate and were found to be enhanced more than 10-fold after the infusion of IL-1 alpha or IL-1 beta. This effect was paralleled by the enhanced pain reflexes and persisted for at least one hour after cessation of the IL-1 perfusion. Both the increased pain reflexes as well as the enhanced PGE2 levels were abolished by addition of the cyclooxygenase inhibitor diclofenac-Na (Voltaren) to the perfusion fluid. These results show that besides the numerous known physiological functions of IL-1, it may also play a role in peripheral pain sensations.

Animals↗
PubMed1987

Arthritis in MRL/LPR mice and in collagen II sensitized DBA-1 mice and their use in pharmacology.

For assessment of anti-arthritic drugs, we used mice of the autoimmune MRL/lpr strain and DBA-1 mice sensitized with collagen type II. Our studies showed that in these two mouse arthritis models, unlike the classical rat adjuvant arthritis, the nonsteroidal antiinflammatory compounds tested were either ineffective or minimally affected a chosen number of humoral parameters and the incidence and severity of arthritis. Interestingly, both arthritis models showed a distinct pharmacological pattern in response to the slow-acting anti-rheumatic drugs, whereas steroids and cyclophosphamide inhibited both arthritic processes. Therefore, these two mouse models are useful for studying the immunopathological events operating in chronic inflammation and could potentially serve the characterization of new antirheumatic drugs.

Animals↗
PubMed1986

Delayed type hypersensitivity (DTH) to type II collagen (CII) in DBA-1 mice.

Sensitization of DBA-1 mice with Type II collagen (CII) in complete Freund's adjuvant can cause polyarthritis. A possible link between CII-induced arthritis and delayed type hypersensitivity (DTH) has been suggested, so we decided to investigate the susceptibility of DBA-1 mice to CII induced DTH reactions. The mice were primed with a dose of 10 micrograms CII i.p. 4 days before challenging with 40 micrograms CII in the ear. Swelling was measured 48 h later and was found to be reproducible. Responsiveness to CII could be transferred with whole spleen cell populations from primed animals or with enriched spleen T cells, thus confirming the cellular nature of the reaction. Lymph node cells from CII/CFA footpad immunized animals were restimulated with CII in vitro. These cells were able to passively transfer DTH sensitivity in vivo and exhibited specificity for this antigen in vitro in proliferation assays.

Animals↗
PubMed1985

A monoclonal antibody to a differentiation antigen present on mature human macrophages and absent from monocytes.

A monoclonal antibody is described that has been generated in the mouse against cultured human blood monocytes/macrophages. The antibody, designated 25F9, belongs to the IgG1 subclass, detects antigens of m.w. 86,000, and does not react with freshly isolated blood monocytes but reacts with monocytes after 3 days of culture. The expression of the 25F9 antigen on macrophages increases with culture time. Furthermore, the antibody is negative on platelets, granulocytes, lymphocytes, and a large number of human cell lines except the two melanoma lines MeWo and Mel 57. In cryostat sections of normal human tissue (skin, lung, liver, thymus) and of inflammatory or neoplastic tissue (cutaneous lymphoma, eczema, BCG-granuloma, and melanoma), the antibody reacts with scattered macrophages in the dermis but not with epidermal Langerhans cells, with alveolar macrophages, with liver Kupffer cells, and with scattered macrophages in the cortex and medulla of thymus. In eczema, BCG-granuloma, and cutaneous lymphoma, only a few infiltrating macrophages were stained. On the other hand, a large number of macrophages and melanophages reacted positively in melanoma. In some cases melanoma cells also stained weakly positive. Thus, the antibody detects a differentiation antigen preferentially expressed on mature, tissue-fixed macrophages and absent from blood monocytes.

Animals↗
PubMed1984

Collection of large quantities of mononuclear cells from individual donors by continuous flow centrifugation leukapheresis.

Continuous flow centrifugation leukapheresis allows the continuous removal of leukocytes from the peripheral blood of individual donors. With the IBM 2997 cell separator, leukapheresis of granulocytes has been well established. On the other hand, no standard procedure for the collection of lymphocytes and/or monocytes has yet been described. Here, we investigated the conditions necessary for collection of large amounts of mononuclear cells with highest possible purity. The average yield from more than 100 healthy donors was 8 X 10(9) leukocytes per donor containing 80-100% mononuclear cells (MNC). Of the MNC, 10-55% were monocytes and 45-90% lymphocytes, depending on the donor. The rotor speed for maximal MNC collection was between 800 and 1000 rpm. Highest yields of monocytes were obtained at 900 rpm. No sedimenting agents were added to the blood. With more than 150 donors no rebound leukocytosis or lasting depression of blood cell counts was observed after leukapheresis. One patient with the Sézary syndrome who was subjected to leukapheresis for 26 months at 3-6 week intervals showed no pathological changes in his blood cell count to date. The disease was stabilized and no abnormalities in resistance to infection became apparent.

Adult↗