bluuebunny/crossref_metadata_2025_split huggingface dataset:
IFN‐γ Inhibits Internalization of Soluble Aminated β‐1, 3‐D‐Glucan by Macrophages and Thereby Down‐Regulates the Glucan Induced Release of TNF‐α: and IL‐1β
Authors: KONOPSKI Z. , SELJELID R , ESKELAND T. 
Published: July 2006

We have previously shown that soluble aminated β‐1, 3‐D‐glucan (AG) and glucan‐derivatized micro‐beads (GDM) bind to the specific β‐glucan receptor on mouse peritoneal macrophages. Phagocytosis of GDM by macrophages is mediated through the β‐glucan receptor. IFN‐γ which increases macrophage phagocytic capacity, also increased the phagocytosis of GDM. In the present study we show that IFN‐γ inhibits Internalization of AG in macrophages in a dose‐ and time‐dependent manner. The inhibitory effect of IFN‐γ was neutralized by treatment of the macrophages with cycloheximide. These results were confirmed by confocal laser scanning microscopy which showed that IFN‐7 treated cells incorporated less fluorescein‐labelled AG than did untreated cells. IFN‐γ did not change the macrophage‐binding capacity for AG showing that the inhibitory effect of IFN‐γ is not caused by decreased number of β‐glucan receptors on the cells. The stimulatory effect of AG on IL‐β and TNF‐α release from macrophages was reduced by pretreatment of the cells with IFN‐γ.We conclude that the uptake of AG and GDM in macrophages, both mediated through the β‐glucan receptor, are differently regulated by IFN‐γ. The reduced internalization of AG after IFN‐γ treatment of macrophages, is probably responsible for the down‐regulation of IL‐1 and TNF‐α secretion.
The Binding of Synovial Tissue‐Derived Human Monoclonal Immunoglobulin M Rheumatoid Factor to Immunoglobulin G Preparations of Differing Galactose Content
Authors: SOLTYS A. J. , HAY F. C. , BOND A. , AXFORD J. S. , JONES M. G. , RANDEN I. , THOMPSON K. M. , NATVIG J. B. 
Published: July 2006

There are several sites on IgG Fc that have been reported to be the epitopes for binding rheumatoid factors (RF). It is now established that there are alterations in the oligosaccharides on IgG from patients with rheumatoid arthritis and it has been suggested that these changes may enhance immune complex and cryoglobulin formation.We have used a series of IgG preparations differing in their content of oligosaccharide chains lacking galactose from 18 to 86% to determine whether changes in sugar content affect the binding of rheumatoid factor. Five of 16 monoclonal rheumatoid factors prepared from synovial tissue, from patients with juvenile or adult rheumatoid arthritis, bound better to IgG which was deficient in galactose. Six of the 16 rheumatoid factors from the same patients bound independently of the galactose content. Four of the 16 rheumatoid factors could not be absolutely grouped in this manner but seemed to demonstrate a preference for agalactosyl IgG. One rheumatoid factor bound better to fully galactosylated IgG. There was an association between enhanced binding to galactosc‐deficient IgG and monoreactivity and a very strong association between the functional affinity of the rheumatoid factors and the dependent binding.
A Rad LV‐Induced γδ T Cell Lymphoma Displaying an Antitumoral Cytotoxicity
Authors: MARTIN‐SIMONET M.‐T. , MARINI V. , RICCIARDI‐CASTAGNOLI P. , ASTIER‐GIN T. , GREIMERS R. , BONIVER J. , SCHAAF‐LAFONTAINE N. 
Published: July 2006

We described previously the induction by RadLV infection of a lymphoma (NS8) expressing a cytolytic activity against an MCA‐induced fibrosarcoma. We report here that the cytolytic activity of these immortalized CD3+, CD8+ T cells is non‐MHC‐restricted. We then determined the structure and expression of the TCR chains expressed by these cells. Only partial rearrangement of the β chain associated to an abnormally short transcript was detected in NS8 cells, whereas the γ chain is rearranged and normally transcribed. On the opposite, rearrangement and expression of these genes were found in the other RadLV‐induced lymphomas analysed. Moreover, γ TCR proteins were detected on the cell surface of NS8 cells only, whereas the αβ complex, presents on the other T cell lines, was not expressed by NS8 cells.The ability of NS8 cells or of cells obtained from activated lymph nodes (harvested from mice grafted with the T2 sarcoma used to induce the NS8 line) to lyse the T2 sarcoma cell line was analysed. With both types of lymphocytes, the cytotoxicity was partially inhibited by a preincubation of the effector cells with anti‐γ antibodies.These results demonstrate that γδ lymphocytes can mediate anti‐tumour cytotoxicity and NS8 lymphoma line may be representative of the TCR γ CD8+ T cell subpopulation expressing non MHC‐restricted cytotoxicity and displaying antitumoral activity.
The Importance of G1m and 2 Allotypes for the IgG2 Antibody Levels and Avidity Against Pneumococcal Polysaccharide Type 1 Within Mono‐ and Dizygotic Twin‐Pairs
Authors: KONRADSEN H. B. , OXELIUS V.‐A. , HAHN‐ZORIC M. , HANSON L. Å. 
Published: July 2006

Eighty‐two mono‐or dizygotic Caucasian twins vaccinated with a 23‐valent pneumococcal vaccine, who had previously had their IgG2 antibody levels to pneumococcus type 1 determined before and after vaccination, were included in this study. Their IgG2 antibody levels were related to their G1m and G2m allotypes/phenotypes and their Gm amounts.Eight different Gm phenotypes were found and characteristically IgG2 antibody levels were related to them. G2m (n) homozygotic twins had significantly higher IgG2 levels than heterozygotic twins who had significantly higher levels than G2m (‐n) homozygotic twins (P <0.05). The G1m allotype, on the other hand was without influence on the IgG2 levels and so were the Gm amounts among G2m (n) heterozygotic twins. The IgG2 antibody avidities were not related to Gm allotypes but significantly correlated to IgG2 levels (P = 0.05). Finally, a highly significant intra‐pair correlation was found for avidity in the monozygotic twins supporting a genetic regulation of avidity (P <0.002).These results may explain our earlier findings that IgG2 antibody levels after pneumococcal vaccination are significantly more closely correlated within mono‐compared to dizygotic twins.
Role of the Bowel Flora for Development of Immunity to hsp 65 and Arthritis in Three Experimental Models
Authors: BJORK J. , KLEINAU S. , MIDTVEDT T. , KLARESKOG L. , SMEDECÅRD G. 
Published: July 2006

An infectious aetiology in rheumatoid arthritis (RA) has for long been suggested, although no conclusive evidence for this is at present available. Lately a large interest has been devoted to the involvement of heat shock proteins (hsps) in autoimmune disorders due to their conserved structure and immunogenic properties. Immunity to hsps has been observed both in human autoimmune conditions and in experimental models of autoimmune disease. We have studied the role of the bacterial flora and hsp immunity in the arthritic response in three experimental models of arthritis; type II collagen arthritis (CIA), adjuvant arthritis (AA) and oil induced arthritis (OIA); by using germ free and conventional DA rats.A high incidence of severe arthritis developed in all the models evaluated irrespectively of whether the animals were in the conventional or germ free state. This confirms earlier results which show a minor effect of the bacterial flora in CIA and AA in high responder strains. These results also show that a severe OIA can develop in germ free animals. Despite the severe arthritic response induced, no serum antibody levels to hsp 65 could be detected in the germ free animals, which was in contrast to the conventional animals where a positive anti‐hsp 65 serum response was seen in 35–80% of the animals with CIA, AA or OIA.These results show that development of a humoral response to hsp 65 in these models of arthritis is dependent on the presence of a bacterial flora. Further, the lack of humoral immunity in germ free animals despite a severe arthritic response indicates that humoral immunity to hsp 65 is not involved in development of disease in these three models of experimental arthritis.
Intraembryonic Haemopoietic Cells and Early T Cell Development
Authors: LAMPISUO M. , KARVINEN J. , ARSTILA T. PETTERI , LASSILA O. 
Published: July 2006

T cell precursors in the chick embryo have been localized into the intraembryonic mesenchyme (IEM) and into the para‐aortic region before the first wave of the thymic colonization on embryonic day (ED) 6, 5–8. The cell surface markers of avian prethymic stem cells are not known. It is also not known whether these precursor cells are already committed to the T cell lineage before their thymic colonization.In 7‐day‐old chick embryos Ov+ cells were found in the para‐aortic region. Also the endothelial cells of the embryonic dorsal aorta were positively stained. Ov antigen might represent a very primitive marker for precursor cells having the potentiality to differentiate both to haemopoietic and endothelial cells. Scattered CD45+ cells were observed in the same para‐aortic area as in many haemopoietic areas in the loose embryonic mesenchymal tissues. CD8α (MoAb 3–298) expressing haemopoielic cells were detected before thymic colonization on ED6. In flow cytometric analysis of IEM precursors Ov, CD45 and CD8α expressing cells seemed to form distinct subsets suggesting heterogeneity of these haemopoietic cells.
A Human Melanoma Cell Line, Recognized by Both HLA Class I and Class II Restricted T Cells, is Capable of Initiating both Primary and Secondary Immune Responses
Authors: OLSEN A. C. , POSSUM B. , KIRKIN A. F. , ZEUTHEN J. , GAUDERNACK G. 
Published: July 2006

We have characterized a melanoma cell line, FM3, established from a metastasis of a 75 year old female patient (HLA–A2, HLA–DQ7) with malignant melanoma. This cell line expresses both HLA class I and class II antigens, as well as several important accessory molecules at high levels. FM3 cells were shown to function as a stimulator of both allogeneic as well as autologous mixed lymphocyte tumour cell culture (MLTC). From these autologous MLTC we were able to generate cytotoxic T cell clones indicating that FM3 is capable of processing and presenting endogenous antigens.We have used this cell line in a model system to investigate whether these cells were able to initiate and support an immune response with specificity for selected peptide antigens. The FM3 cell line was capable of presenting a HLA–DQ7 restricted ras derived peptide (5–21, 13Gly–Asp) to a previously established T cell clone, RM70. The ability of FM3 to function as an antigen presenting cell (APC) was comparable to that of an autologous Epstein Barr virus (EBV) transformed B cell line. The CD4+ T cell clone RM70 showed a peptide–specific anti–proliferative effect on FM3 cells. This growth inhibition was not due to cytotoxicity as measured in a standard 4h chromium release assay. The FM3 cell line also presented a HLA–A2 restricted nonapeptide derived from the influenza matrix protein. M 1 (58–66) to a CD8+ T cell line specific for this peptide. This resulted in an effective killing of the melanoma cells.Together, these data suggest that some melanomas may initiate an immune response by presenting their own specific antigens in an immunogenic context, and subsequently serve as targets for T cells of both the CD4+ and CD8+ phenotype.
Subclass Distribution of IgA and IgG Antibodies Against Clq in Patients with Rheumatic Diseases
Authors: COREMANS I. E. M. , DAHA M. R. , VAN DER VOORT E. A. M. , SIEGERT C. E. H. , BREEDVELD F. C. 
Published: July 2006

To obtain insight into the immunoregulatory mechanisms in patients with different rheumatic diseases, the occurrence and the subclass distribution of IgA and IgG antibodies against Clq (anti‐ClqAb) was determined. In patients with systemic lupus erythaematosus (SLE) the highest frequency of increased serum levels of IgG anti‐ClqAb were found, whereas IgA anti‐ClqAb were predominantly present in patients with ankylosing spondylitis (AS) and patients with rheumatoid arthritis complicated by vasculitis (RV). In all the IgA anti‐ClqAb positive AS and RV patients the antibody reactivity involved the IgAl subclass while the IgA2 subclass was found in 47% of the patients. Further characterization of the IgA anti‐Clq binding activity in sera of AS patients revealed that both subclasses of IgA anti‐ClqAb were predominantly polymeric; the binding of both IgA subclasses with solid phase CI q was inhibitable by aggregated fluid phase Clq; we found no delectable interference of rheumatoid factor in the test system for the measurement of IgA anti‐ClqAb. In patients with SLE the IgG anti‐ClqAb reactivity was mainly of the IgG2 and IgG3 subclass, whereas in the same patients the IgG anti‐tetanus toxoid response was not restricted to these subclasses.The predominance of IgG2 and IgG3 subclass of anti‐ClqAb in sera of SLE patients, suggests a skewing of the anti‐ClqAb response. The observation that the IgA anti‐ClqAb of both subclasses is predominantly polymeric in nature and the notion that polymeric IgA is associated with activation of inflammation cascades, suggests that IgA anti‐ClqAb may contribute to tissue damage.
First Evidence for the Existence of Multiple Isoforms of Bovine Serum Amyloid‐A (apoSAA)
Authors: ALSEMGEEST S. P. M. , HORADAGODA A. , HULSKAMP‐KOC C. K. , TOOTEND P. C. J. , KIM H. , NIEWOLD TH. A. , GRUYS E. 
Published: July 2006

Bovine serum amyloid‐A (SAA) was purified from acute‐phase high density iipoprotein (HDL) by affinity chromatography and subsequent gel filtration chromatography. The identity of the isolated protein was checked by Western blotting following SDS‐urea‐PAGE using antisera raised against the purified protein fraction (SAA) and Amyloid A (AA). The antiserum raised against the purified SAA stained Congo red positive regions in the kidney of an AA‐amyloidotic cow and reacted on Western blot with an AA‐related protein of approximately 14kDa. Moreover, it immunostained two to three bands, of approximately 14kDa, present in serum from diseased cows, proportionally to the serum SAA concentration as measured by ELISA.Isoelectric focusing of the purified bovine SAA fraction revealed three major (pI 5.5, 6.0, 6.4) and three minor (pi 4.8, 5.0, 7.3) isoforms and two‐dimensional SDS‐urea‐PAGE confirmed the identity of the major isoforms. Isoelectric focusing of SAA isolated from sera, obtained from cows affected with different diseases, showed a variable ratio of the isoforms. In SAA isolated from serum obtained from acow suffering from spontaneous AA‐amyloidosis only one isoform (pI 4.8) was detectable.It is concluded that the results give first evidence for the existence of multiple isoforms of bovine SAA, occurring in different plasma concentration ratios during different diseases.
TNF‐α Dominates Cytokine mRNA Expression in Lymphoid Tissues of Rats Developing Collagen‐ and Oil‐Induced Arthritis
Authors: MÜSSENER Å. , KLARESKOG L. , LORENTZEN J. C. , KLEINAU S. 
Published: July 2006

Experimental arthritis can be induced in the DA rat strain with rat type II collagen (RCII) administered in Freund's incomplete adjuvant oil (FIA) or with only FLA. If ovalbumin (Ova), is added to these arthritogens the development of arthritis is blocked. To investigate the mechanisms responsible for induction of arthritis, as well as inhibition of arthritis, a kinetic study of the local cytokine expression in lymph nodes has been performed after immunization with the above mentioned agents. By using in situ hybridization techniques, mRNA expression of TNF‐α, IL‐2, IFN‐γ and IL‐4 was determined. The results show a rapid and pronounced accumulation of TNF‐α mRNA expression, in RCII/FIA and FIA immunized rats. This pronounced expression of TNF‐α mRNA was not recorded in the Ova/FIA immunized animals, which instead were the only animals in which the IL‐4 gene was expressed. The expression of IFN‐γ mRNA was limited in RCII/FIA‐ and FIA‐immunized rats, whereas IL‐2 mRNA expression was detected only after RCII/FIA injection. Lymph node cells from RCII‐immunized animals generated a high amount of TNF‐α mRNA after restimulation with RCII, whereas restimulation with the mitogen Con A generated a cytokine mRNA response dominated by IL‐2 and IFN‐γ.These and other results indicate that a strong local expression of TNF‐α, induced by arthritogenic stimuli, may be important for the induction of arthritis. Moreover, the elicitation of an immune reaction against Ova, may inhibit arthritis development by contributing to a shift in the initial arthritogenic cytokine response.
Arabidopsis cpFtsY mutants exhibit pleiotropic defects including an inability to increase iron deficiency‐inducible root Fe(III) chelate reductase activity
Authors: Durrett Timothy P. , Connolly Erin L. , Rogers Elizabeth E. 
Published: July 2006

SummaryAll plants, except for the grasses, must reduce Fe(III) to Fe(II) in order to acquire iron. In Arabidopsis, the enzyme responsible for this reductase activity in the roots is encoded by FRO2. Two Arabidopsis mutants, frd4‐1 and frd4‐2, were isolated in a screen for plants that do not induce Fe(III) chelate reductase activity in their roots in response to iron deficiency. frd4 mutant plants are chlorotic and grow more slowly than wild‐type Col‐0 plants. Additionally, frd4 chloroplasts are smaller in size and possess dramatically fewer thylakoid membranes and grana stacks when compared with wild‐type chloroplasts. frd4 mutant plants express both FRO2 and IRT1 mRNA normally in their roots under iron deficiency, arguing against any defects in systemic iron‐deficiency signaling. Further, transgenic frd4 plants accumulate FRO2‐dHA fusion protein under iron‐deficient conditions, suggesting that the frd4 mutation acts post‐translationally in reducing Fe(III) chelate reductase activity. FRO2‐dHA appears to localize to the plasma membrane of root epidermal cells in both Col‐0 and frd4‐1 transgenic plants when grown under iron‐deficient conditions. Map‐based cloning revealed that the frd4 mutations reside in cpFtsY, which encodes a component of one of the pathways responsible for the insertion of proteins into the thylakoid membranes of the chloroplast. The presence of cpFtsY mRNA and protein in the roots of wild‐type plants suggests additional roles for this protein, in addition to its known function in targeting proteins to the thylakoid membrane in chloroplasts.
Arabidopsis MAP kinase 4 regulates salicylic acid‐ and jasmonic acid/ethylene‐dependent responses via EDS1 and PAD4
Authors: Brodersen Peter , Petersen Morten , Bjørn Nielsen Henrik , Zhu Shijiang , Newman Mari‐Anne , Shokat Kevan M. , Rietz Steffen , Parker Jane , Mundy John 
Published: July 2006

SummaryArabidopsis MPK4 has been implicated in plant defense regulation because mpk4 knockout plants exhibit constitutive activation of salicylic acid (SA)‐dependent defenses, but fail to induce jasmonic acid (JA) defense marker genes in response to JA. We show here that mpk4 mutants are also defective in defense gene induction in response to ethylene (ET), and that they are more susceptible than wild‐type (WT) to Alternaria brassicicola that induces the ET/JA defense pathway(s). Both SA‐repressing and ET/JA‐(co)activating functions depend on MPK4 kinase activity and involve the defense regulators EDS1 and PAD4, as mutations in these genes suppress de‐repression of the SA pathway and suppress the block of the ET/JA pathway in mpk4. EDS1/PAD4 thus affect SA–ET/JA signal antagonism as activators of SA but as repressors of ET/JA defenses, and MPK4 negatively regulates both of these functions. We also show that the MPK4–EDS1/PAD4 branch of ET defense signaling is independent of the ERF1 transcription factor, and use comparative microarray analysis of ctr1, ctr1/mpk4, mpk4 and WT to show that MPK4 is required for induction of a small subset of ET‐regulated genes. The regulation of some, but not all, of these genes involves EDS1 and PAD4.
The Arabidopsis pex12 and pex13 mutants are defective in both PTS1‐ and PTS2‐dependent protein transport to peroxisomes
Authors: Mano Shoji , Nakamori Chihiro , Nito Kazumasa , Kondo Maki , Nishimura Mikio 
Published: July 2006

SummaryPeroxisome biogenesis requires various complex processes including organelle division, enlargement and protein transport. We have been studying a number of Arabidopsis apm mutants that display aberrant peroxisome morphology. Two of these mutants, apm2 and apm4, showed green fluorescent protein fluorescence in the cytosol as well as in peroxisomes, indicating a decrease of efficiency of peroxisome targeting signal 1 (PTS1)‐dependent protein transport to peroxisomes. Interestingly, both mutants were defective in PTS2‐dependent protein transport. Plant growth was more inhibited in apm4 than apm2 mutants, apparently because protein transport was more severely decreased in apm4 than in apm2 mutants. APM2 and APM4 were found to encode proteins homologous to the peroxins PEX13 and PEX12, respectively, which are thought to be involved in transporting matrix proteins into peroxisomes in yeasts and mammals. We show that APM2/PEX13 and APM4/PEX12 are localized on peroxisomal membranes, and that APM2/PEX13 interacts with PEX7, a cytosolic PTS2 receptor. Additionally, a PTS1 receptor, PEX5, was found to stall on peroxisomal membranes in both mutants, suggesting that PEX12 and PEX13 are components that are involved in protein transport on peroxisomal membranes in higher plants. Proteins homologous to PEX12 and PEX13 have previously been found in Arabidopsis but it is not known whether they are involved in protein transport to peroxisomes. Our findings reveal that APM2/PEX13 and APM4/PEX12 are responsible for matrix protein import to peroxisomes in planta.
The central coiled‐coil domain and carboxyl‐terminal WD‐repeat domain of Arabidopsis SPA1 are responsible for mediating repression of light signaling
Authors: Yang Jianping , Wang Haiyang 
Published: July 2006

SummaryArabidopsis constitutive photomorphogenic 1 (COP1) is an E3 ubiquitin ligase that directly binds and targets for degradation a number of photomorphogenesis‐promoting transcription factors, including HY5 and HFR1, to desensitize light signaling. Arabidopsis suppressor of phyA‐105 (SPA1), which encodes a protein structurally related to COP1, also acts to repress photomorphogenesis under various light conditions. Here we show that overexpression of Arabidopsis SPA1 results in a hyperetiolation phenotype and reduced accumulation of HY5 and HFR1. In addition, we show that both COP1 and SPA1 are each dependent on the presence of the other for their repressive effect on light signaling. Moreover, we demonstrate that both the central coiled‐coil and the C‐terminal WD‐repeat domains of SPA1 are necessary, and together these two domains are sufficient for repressing photomorphogenesis. However, the N‐terminal kinase‐like domain of SPA1 contributes to its full activity and promotes destabilization of the SPA1 protein. Together, our results substantiate the notion that COP1 and SPA1 act in concert to form a functional E3 ubiquitin ligase complex and provide a molecular basis for understanding the structure–function relationship of SPA1.