bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of interferon-gamma-mediated activation in mouse macrophages treated with lipoarabinomannan
Authors: SIBLEY L D , ADAMS L B , KRAHENBUHL J L 
Published: July 2010

SUMMARYLipoarabinomannan (LAM), purified from the cell walls of Mycobacterium leprae and M. tuberculosis, is a potent inhibitor of interferon-gamma (IFN-γ) mediated activation of macrophages. The capability of LAM to inhibit IFN-γ activation of macrophages in vitro was dose dependent and required a 24-h pre-exposure. Defective activation was evident as a block in IFN-γ-induced cytocidal activity for tumour cell targets and microbicidal capacity for intracellular Toxoplasma gondii. Additionally, LAM treatment blocked the induction of surface la antigens on peritoneal macrophages by IFN-γ. The requirement for pretreatment with LAM was further substantiated by the finding that peritoneal macrophages that were activated in vivo were not affected by LAM treatments and retained full microbicidal function. However, once inhibited by LAM treatment in vitro, macrophages remained fully refractory to IFN-gamma; activation for up to 5 days in culture. Inhibition of IFN-γ activation in macrophages treated with LAM was not overcome by 100-fold increases in the dose of IFN-γ used or by a constant dose of IFN-γ in combination with 100-fold increases in the level of endotoxin used to trigger cytotoxic activity. The defect in IFN-γ unresponsiveness was not due to altered receptor function, as control and LAM-treated macrophages showed similar capacity to bind, internalize, and digest radiolabelled IFN-γ. Based on the in vitro findings reported here, the inhibition of IFN-γ-mediated macrophage activation by exposure to LAM may contribute to defective macrophage function observed in lepromatous granulomas and thus constitutes an important aspect of pathogenesis in mycobacterioses.
Interleukin-6 and ACTH act synergistically to stimulate the release of corticosterone from adrenal gland cells
Authors: SALAS M A , EVANS S W , LEVELL M J , WHICHER J T 
Published: July 2010

SUMMARYWe investigated whether interleukin-6 (IL-6) could cause the release of corticosterone by a direct interaction with the adrenal gland. Primary cultures of rat adrenal glands were obtained by dispersion with collagenase and incubated for 24 h with different doses of IL-6. Levels of corticosterone were measured by competitive protein binding assay. A significant (P&lt; 0.025) dose-dependent increase in corticosterone levels was seen at all doses used. Time course experiments demonstrated that IL-6 stimulated corticosterone release over a period of 24 h but not after 12 or 3 h. The stimulation of adrenal cells with different doses of ACTH1–24 and 40 U/ml of IL-6 showed a synergistic effect when IL-6 was combined with low concentrations of ACTH1–24 (2 and 20 pmol/l). This effect was not evident at higher doses. Our results suggest that IL-6 may act at different levels of the hypothalmic pituitary adrenal axis. Moreover the finding of a synergistic effect with ACTH1–24 indicates that IL-6 could play a role in the long term response to stress.
Transforming growth factor-β1 in rheumatoid synovial membrane and cartilage pannus junction
Authors: CHU C Q , FIELD M , ABNEY E , ZHENG R Q H , ALLARD S , FELDMANN M , MAINI R N 
Published: July 2010

SUMMARYTransforming growth factor (TGF)-β has been shown to promote tissue repair and have immunosuppressivc actions, and has been proposed to have a role in rheumatoid arthritis (RA). Using immunohistochemical techniques with rabbit F(ab′)2 antibodies raised against recombinant human TGF-β1, we have detected TGF-β1 in the synovial tissue and cartilagc/pannus junction (CPJ) from 18/18 patients with RA. TGF-β1 was found predominantly in the thickened synovial lining layer in RA. but also detected in a peri vascular pattern in the synovial interstitium as well as in occasional cells in the lymphoid aggregates. At the CPJ it was found both in cells at the distinct junction as well as in the transitional region of the diffuse fibroblastic zone. The cells staining for TGF-β1 were identified by double immunofluorcsccnce staining as being from the monocy te/macrophage scries as well as the type B synovial lining cells. TGF-β1 was also detected in the synovial membrane sections from 4/4 patients with systemic lupus erythematosus/mixed connective tissue disease and 5/8 patients with osteoarthri-tis, in a similar distribution to that seen in RA, and in the lining layer of 1/7 normal synovial membranes. These results add to histological evidence confirming that TGF-/β1 is present in RA synovial cells and those from otherarthritides. The distributions of TGF-/β1 in RA synovial membrane reflects its known actions, as it can be detected at the CPJ, where it could induce repair, and close to activated cells upon which it may exert an immunosuppressivc action.
Extracellular organelles (prostasomes) are immunosuppressive components of human semen
Authors: KELLY R W , HOLLAND P , SKIBINSKI G , HARRISON C , MCMILLAN L , HARGREAVE T , JAMES K 
Published: July 2010

SUMMARYNumerous reports have ascribed immunosuppressive activity to human seminal plasma and there is growing agreement that much of this activity can be accounted for by the very high levels of E series prostaglandins present (up to 300 μm 19-hydroxy prostaglandin E). However not all suppressive activity is due to prostaglandin since several reports have appeared of high molecular weight active substances and we have found that stripped seminal plasma is still effective in inhibiting the mitogen-induced proliferation of lymphocytes. In this study such immunosuppressive activity has been separated by molecular size fractionation and the activity has been found to be particulate and corresponded to the previously reported prostasomes. These are trilaminar to multilaminar vesicles (150 nm diameter) which are secreted by the prostate. Pure preparations of prostasomes inhibited mitogen-induced lymphoproliferation in a dose-dependent manner with a concentration of prostasomes equivalent to 40% of that seen in seminal fluid giving 69% suppression of thymidine incorporation. The suppressive activity survived boiling and therefore was unlikely to be due to enzymatic action associated with these organdies. Interaction with the accessory cells, involved in full development of the lymphoproliferation induced by mitogen, was indicated and this possibility was supported by the demonstration of a direct effect of prostasomes on macrophage function using a mouse macrophage cell line. The prostasomes in semen may play a complementary role to the prostaglandins in neutralizing the immune defences of the female reproductive tract. This combination would allow the alloantigenic spermatozoa the best chance of achieving fertilization, but at the same time leave the recipient open to any infection present in the semen.
Expression of rheumatoid factor associated cross-reactive idiotopes by glandular B cells in Sjögren's syndrome
Authors: DEACON E M , MATTHEWS J B , POTTS A J C , HAMBURGER J , MAGEED R A , JEFFERIS R 
Published: July 2010

SUMMARYB cell expression of the germline gene-encoded, kappa IIIb-associated, rheumatoid factor (RF) cross-reactive idiotope (CRI) 17–109 and three VHI associated RF CRIs (G6, G8, H1) was investigated immunocytochemically in labial salivary glands from nine patients with primary and six with secondary Sjögren's syndrome, and in inflamed submandibular salivary glands from 10 patients with no history of connective tissue disease. Expression of CRIs by B cell infiltrates in labial glands from patients with primary and secondary Sjögren's syndrome were similar. Lymphoid infiltrates of labial glands from Sjögren's syndrome patients contained a higher proportion of kappa III+ cells reactive for the kappa IIIb-associated 17–109 idiotope (P&lt;0.01) and larger G6 (P&lt;0.02) and HI (P&lt;0.01) positive B cell populations than those within inflamed submandibular salivary glands. Furthermore, in labial glands there was a significant correlation between numbers of 17–109 and G6 idiotope reactive cells (r = 0.61; P &lt; 0.02), reflecting the known association between these H and L chain CRIs in RF IgM paraproteins. These results indicate that B cells bearing both VkIII and VHI-associated CRI are increased in the glandular infiltrates in Sjögren's syndrome and support the idea that this condition is associated with proliferation of immature B cell clones retaining germ-line V genes.
Inhibition of lymphocyte proliferation by a monoclonal antibody (RFT2) against CD7
Authors: COSTANTINIDES Y , KINGSLEY G , PITZALIS C , PANAYI G S 
Published: July 2010

SUMMARYThe effect of the monoclonal antibody RFT2, directed against CD7, on T cell proliferation in unseparated peripheral blood mononuclear cell populations induced by various stimulants was investigated. The addition of RFT2 to cell cultures inhibited the T cell proliferation induced by tuberculin PPD and OKT3 but not by phytohaemagglutinin, concanavalin. A or phorbol myristic acid; RFT2 had to be present during the first 24 h of culture in order to elicit inhibition; inhibition of proliferation was not due to down regulation of interleukin-2 receptor on the surface of T cells; and suppressive effects could be transferred by mononuclear cells prc-treated with RFT2- These results are of particular relevance in view of the known in rivo suppressive effect of RFT2 in humans.
Lymphokine-activated killer (LAK) cells modulate the effects of IL-2 on a T cell-mediated immune response
Authors: MCCULLOCH P , GALLAGHER G , WALSH L P , ZALOOM Y , XIE J 
Published: July 2010

SUMMARYThe ability of LAK cells and/or IL-2 to affect the course of an established T cell response was examined in a delayed-type hypersensitivity (DTH) model. IL-2 greatly increased the magnitude of the response at 24 h, while LAK cells alone had no effect. The administration of LAK cells and IL-2 together also had no effect on the magnitude of the DTH response, demonstrating that LAK cells were able to remove the enhancement seen with IL-2 alone. The presence of LAK cells reduced the serum half-life of IL-2 significantly, but not to an extent able to account for the observed loss of IL-2 induced DTH enhancement. IL-2 administration influenced cell phenotypes in the spleen and draining lymph nodes (DLN), as well as increasing splenic weight; the additional presence of LAK cells markedly altered these effects of IL-2 in the spleen (but not the DLN). Taken together, these results suggest that LAK cells interact with activated T-cells within the immune system and modulate their function.
Specific recognition pattern of IgM and IgG antibodies produced in the course of experimental paracoccidioidomycosis
Authors: VAZ C A C , MACKENZIE D W R , HEARN V M , CAMARGO Z P , SINGER-VERMES L M , BURGER E , CALICH V L G 
Published: July 2010

SUMMARY
Specific IgM and IgG responses to Paracoccidioides brasiliensis produced in resistant and susceptible mice during experimental paracoccidioidomycosis were examined by the immunoblotting procedure. Sera from infected mice recognized 51 antigen bands with apparent molecular masses From 8 to 86 kD. Sixteen of these were defined as major antigen bands because of almost universal presence of antibodies to them, and their intense staining. All sera, including those from normal control mice, tested for both IgM and IgG antibody reacted with the major E antigen which appeared as a large diffuse band from 43 to 47 kD. Comparisons between resistant and susceptible mice showed some significant differences in IgM responses to many antigen bands. While IgG responses were quite similar for both strains, differences were apparent in the response to the antigens at 62 and 68 kD.
Antineutrophil cytoplasmic antibodies (ANCA) directed against cathepsin G in ulcerative colitis, Crohn's disease and primary sclerosing cholangitis
Authors: HALBWACHS-MECARELLI L , NUSBAUM P , NOËL L H , REUMAUX D , ERLINGER S , GRÜNFELD J P , LESAVRE P 
Published: July 2010

SUMMARYAutoantibodies directed against polymorphonuclear neutrophils (PMN) have been observed in serum from patients with ulcerative colitis (UC), Crohn's disease (CD) and primary sclerosing cholangitis (PSC) using indirect immunofluorescence and fixed granulocyte ELISA. Our study demonstrates the presence in the serum of these patients of autoantibodies which bind to an azurophilic granule component distinct from proteinase 3, elastase and myeloperoxidase. These autoantibodies thus belong to the ANCA family, but their antigen specificity differs from the already characterized ANCA antigens. We have found that the same ANCA antigen target, named UC-antigen, was recognized by serum IgG from patients with UC, CD and PSC. It was purified by Matrex Gel Orange A dye affinity chromatography and subsequent immunoabsorption of contaminant proteinase 3 with immobilized anti-proteinase 3 MoAb. The identity between this UC antigen and cathepsin G was demonstrated by their coelution from Matrex Gel Orange A column and the parallel titration of cathepsin G-specific enzymatic activity and UC ANCA binding, both in partially purified UC antigen and in highly pure cathepsin G. Furthermore, the use of cathepsin G ELISA confirmed that UC, CD and PSC patients' IgG did indeed bind to cathepsin G. Comparison of the results obtained with azurophilic granule- and cathepsin G-ELISA as well as inhibition of ANCA binding by anti-cathepsin G polyclonal antibodies, revealed that in some patients cathepsin G is the main azurophilic granule target of ANCA while others have other ANCA specificities. The fact that UC, CD and PSC are frequently associated with cathepsin G ANCA, while rarely occurring in other types of vasculitis, is intriguing but suggests that these diseases may have a common pathogenetic mechanism.
Antigen-specific T cell recognition of affinity-purified and recombinant thyroid peroxidase in autoimmune thyroid disease
Authors: EWINS D L , BARNETT P S , RATANACHAIYAVONG S , SHARROCK C , LANCHBURY J , McGREGOR A M , BANGA J P 
Published: July 2010

SUMMARYTheTcell proliferative responses of peripheral blood lymphocytes from 20 patients with autoimmune thyroid disease (AITD) and 20 healthy controls were analysed to immunoaffinity-purified thyroid peroxidase (TPO) and recombinant antigen preparations generated in Escherichia coli as glutathione-s-transferase fusion proteins. The epitope specificity of the T cell response was investigated using a selection of eight discrete recombinant fragments encompassing the whole of the extracellular region of the TPO molecule. Significant differences in the proliferative responses between patients and controls were observed to the full length, affinity-purified TPO molecule (P &lt; 0·002) as well as to the recombinant fragments Rlc (residues 145–250)(P&lt;0·001) and R2b(residues 457–589)(P&lt;0·001) suggesting the presence of at least two distinct T cell determinants on this autoantigen. One of these T cell epitopes, localized within the region Rlc, has not previously been identified by studies with synthetic peptides.
HLA-associated susceptibility to HIV-1 infection
Authors: FABIO G , SCORZA R , LAZZARIN A , MARCHINI M , ZARANTONELLO M , D'ARMINIO A , MARCHISIO P , PLEBANI A , LUZZATI R , COSTIGLIOLA P 
Published: July 2010

SUMMARY
We studied HLA antigen distribution of 50 heterosexual partners of HIV+ drug abusers with more than I year of sexual exposure to HIV, 36 children born to seropositive mothers and 61 haemophiliac patients exposed to presumably infectious clotting factor concentrates. B52 and B44 antigens were associated with HIV resistance while B51 was associated with HIV susceptibility. Forty-nine HIV+ drug abusers, spouses of heterosexual partners studied and 25 HIV+ mothers of the children were also typed. DR11 phenotype was associated with infectiousness of HIV+ subjects. Our data suggest that the HLA region controls susceptibility to infection with HIV and infectiousness of HIV+ subjects in different risk groups.
Abnormal production of B cell growth factor in patients with systemic lupus erythematosus
Authors: OGAWA N , ITOH M , GOTO Y 
Published: July 2010

SUMMARYIn order to clarify the role of B cell growth factor (BCGF) in the pathogenesis of systemic lupus erythematosus(SLE), BCGF production by peripheral blood mononuclear cells(PBMC) and T cells was studied using a new bioassay for BCGF activity. For this purpose, we established an Epstein-Barr (EB) virus-transformed B cell line KS-3.F10 that proliferates only in response to two B cell-specific BCGF, low-mol. wt BCGF (LMW-BCGF) and high-mol. wt BCGF (HMW-BCGF). PBMC from active SLE patients produced less BCGF when stimulated with phytohaemagglutinin (PHA) compared with controls. The decreased BCGF production by PHA-stimulated PBMC from active SLE reverted to control values when SLE became inactive. However, PHA-stimulated T cells from active SLE patients produced more BCGF compared with controls, whereas those from inactive SLE showed normal BCGF production. Spontaneous BCGF production by T cells was not observed in active SLE patients. These findings suggest that decreased BCGF production by SLE PBMC is due to excessive BCGF consumption by B cells in vitro and that SLE T cells produce large amounts of BCGF with appropriate immune stimuli in vitro to promote polyclonal B cell activation.
Cellular immune response to the cell walls ofMycobacterium lepraein leprosy patients and healthy subjects exposed to leprosy
Authors: ROCHE P W , NEUPANE K D , BRITTON W J 
Published: July 2010

SUMMARYCell walls of M. leprae consist of complex arrangements of carbohydrate, lipid, peptidoglycan and protein molecules. Recently, extractable proteins of a wide range of molecular weights were identified as components of the cell wall. We have examined the cellular immune responses of Nepali leprosy patients to a cell wall preparation of M. leprae enriched for these proteins. Strong lymphocyte proliferative responses to the antigens were present in half of the paucibacillary leprosy patients and in the majority of healthy control subjects with occupational exposure to leprosy. Patients with multi-bacillary disease responded poorly and patients with tuberculosis had intermediate responses. Proliferative responses to the cell wall protein fraction were strongly correlated to the proliferative responses to sonicates of the whole leprosy bacillus. Immunization of mice with cell wall proteins resulted in inhibition of growth of M. leprae following foot-pad inoculation with viable organisms. Therefore cell-mediated immune responses to the extractable proteins of the cell wall may play a role in protective immunity against M. leprae infection.
Identification of DNA-binding proteins on human umbilical vein endothelial cell plasma membrane
Authors: CHAN T M , FRAMPTON G , CAMERON J S 
Published: July 2010

SUMMARYThe binding of anti-DNA antibodies to the endothelial cell is mediated through DNA, which forms a bridge between the immunoglobulin and the plasma membrane. We have shown that 32P-labelled DNA bound to the plasma membrane of human umbilical vein endothelial cells (HUVEC) by a saturable process, which could be competitively inhibited by non-radiolabelled DNA. In addition, DNA-binding was enhanced in HUVEC that had been treated with IL-1α or tumour necrosis factor-alpha (TNF-α). DNA-binding proteins of mol. wt 46000, 92000, and 84000 were identified by the binding of 32P-labelled DNA to plasma membrane proteins separated on SDS PAGE. DNA-binding proteins of mol. wt 46000 and 84000 were also present in the cytosol and nucleus. Murinc anti-DNA MoAb 410 bound to a single band, at mol. wt 46000, of plasma membrane protein, in the presence of DNA. Our results showed that DNA-binding proteins are present in different cellular fractions of endothelial cells. DNA-binding proteins on the cell membrane could participate in the in situ formation of immune deposits: and their presence in the cell nucleus suggests a potential role in the modulation of cell function.
Regulation of endothelial adhesion molecules by ligands binding to the scavenger receptor
Authors: PALKAMA T , MAJURI M-L , MATTILA P , HURME M , RENKONEN R 
Published: July 2010

SUMMARYMonocyte adherence to the endothelium, their penetration to the subendothelial space and excessive lipid accumulation (foam cell formation) are the initial events in atherogenesis. Scavenger receptors have been reported to play an important role in foam cell formation, since modified low density lipoproteins can be taken up via scavenger receptors in a non-down-regulated fashion. In this study we demonstrate that stimulation of scavenger receptors in endothelial cells induces the expression of endothelial adhesion molecules. Polyinosinic acid (poly I), a known scavenger receptor ligand, significantly induced the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin on human umbilical vein endothelial cells when compared with polycytidylic acid (poly C), a structurally related compound to poly I, which does not bind to the scavenger receptor. The effect of scavenger receptor ligands on the endothelial cell line EA hy. 926 was also tested. Poly I up-regutated ICAM-1 expression also on EA hy. 926 cells, whikit had no effect on IL-lβ or tumour necrosis factor-alpha (TNF-α) production on the same cell line. Poly I-induced ICAM-1 expression on EA hy. 926 cells could be inhibited by H7, a protein kinase C inhibitor, while HA 1004, a preferential protein kinase A inhibitor, had no effect on ICAM-1 expression. The role of protein kinase C in scavenger receptor-mediated adhesion molecule up-regulation was confirmed by the ability of poly I to directly activate protein kinase C, when measured with 3H-phorbol dibutyrate binding to EA hy. 926 cells, while poly C again was ineffective.
Rheumatoid factors from patients with rheumatoid arthritis react with Des-Lys58 -β2m, modified β2-microglobulin
Authors: WILLIAMS R C , NISSEN J R M H , MALONE C C 
Published: July 2010

SUMMARYTen polyclonal IgM rheumatoid factor (RF) preparations, affinity-purified from IgG columns, from patients with rheumatoid arthritis were studied for their ELISA reactivity with native β2m in parallel with Lys58-cleaved β2m and Des-Lys58-β2m, the latter representing cleavage products of the native molecule present in some pathologic human sera. Most RF showed positive reactions with the native form of β2m but reduced reactivity for the cleaved forms of β2m. Reactions between cleaved β2m and RF, in solution, were demonstrated by inhibition of RF binding to native β2m by prcincubation with a range of concentrations of Dcs-Lys58-β2m. By contrast, eight of nine murine MoAbs to human β2m showed approximately equivalent binding to native β2m, Lys58-cleaved β2m, and Des-Lys58-β2m. Reactions between individual human RF and the altered forms of β2m (Lys58-cleaved β2m and Des-Lys58-β2m) appeared to parallel the previously determined β2m single ammo acid specificities, in that RF’ showing strong reactivity with Lysine 58 also showed a significant diminished reactivity with the Des-Lys58-β2m lacking the critical lysine residue. The present studies demonstrate that while human RF react with Lys58-cleaved β2m or Des-Lys58-β2m, preferential reactivity is observed for native unaltered β2m.