bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-2 signalling in T and natural killer (NK) cells associated with their class I-non-restricted killing activity
Authors: Yoneda K , Osaki T , Yamamoto T 
Published: November 2003

Abstract
The signal transduction of IL-2 in NK cells and T cells was compared. On 5 min incubation of these cells  with IL-2, we observed tyrosine phosphorylation of 105-kD and 110-kD proteins in NK cells and of 95-kD and 110-kD proteins in T cells. The phosphorylation reached maximal levels in 15 min in both NK and T cells, but the levels were higher in NK cells, which showed superior killing against Daudi cells. With this phosphorylation, p52shc was also tyrosine-phosphorylated and p21ras was activated by the short term (10 min) treatment of NK and T cells with IL-2. These signals were completely suppressed by anti-IL-2Rβ MoAb, but only slightly suppressed by anti-IL-2Rα MoAb, correlated with the suppression of the class-I-non-restricted cytotoxic activity of NK and T cells by these MoAbs. When tyrosine phosphorylation was inhibited by herbimycin A and genistein, the cytotoxic activities of NK and T cells were nearly completely suppressed. In addition, the tyrosine phosphorylation of JAK3 by IL-2 was more prominent in NK cells than in T cells, but JAK1, JAK2, STAT1α, STAT2 and STAT3 were not phosphorylated. These results indicate that the IL-2 signal flows downstream via both ras-dependent and ras-independent pathways and that the superior killing activity of NK cells depends on their high susceptibility to protein tyrosine phosphorylation by IL-2.
In vivo effects of cytokines on psoriatic skin grafted on nude mice: involvement of the tumour necrosis factor (TNF) receptor
Authors: Gilhar A , David M , Kalish R S , Weisinger G 
Published: November 2003

Abstract
Following engraftment of human involved psoriatic skin to nude mice there is a partial normalization of pathology associated with a loss of inflammatory leucocytes. However, the epidermis remains hyperproliferative, which may reflect a primary defect. The roles of TNF-α, IL-1 and IL-6 in epidermal hyperproliferation of grafted psoriatic lesions were investigated. Before and after treatment, grafts were analysed to determine epidermal thickness and labelling index (LI). HLA-DR, intercellular adhesion molecule-1 (ICAM-1), and TNF receptor (TNF-R; p75 and p55) expression were determined by immunoperoxidase staining. Psoriatic epidermis was found consistently to be negative for p55 TNF-R and p75 TNF-R before grafting. Following engraftment, TNF-R-positive cells (i.e. p55 by keratinocytes; p75 by epidermal dendritic cells) were identified throughout the epidermis. Higher numbers of p75 TNF-R epidermal dendritic cells were found in grafts following a course of TNF-α, IL-6 or IL-1 treatment. The p55 form of the TNF-R expressed by keratinocytes was significantly elevated after treatment with TNF-α or IL-6. HLA-DR and ICAM-1 were also expressed in these grafts. TNF-α, anti-IL-1, and anti-IL-6 treatment induced a marked decrease in the epidermal thickness and LI of psoriatic graft tissue, correcting the hyperproliferation associated with psoriatic epidermis. Supraphysiological levels of TNF-α may saturate and consequently down-regulate their own receptors, leading to a paradoxical inhibitory effect.
Inhibitory effect of salmeterol on the respiratory burst of adherent human neutrophils
Authors: Ottonello L , Morone P , Dapino P , Dallegri F 
Published: November 2003

Abstract
Human neutrophils, plated in fibronectin-coated wells and stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP), were found to undergo a massive and prolonged respiratory burst, as measured by monitoring superoxide production. The β2-agonist salmeterol inhibited the respiratory burst in a dose-dependent manner. In contrast, salbutamol was ineffective. Moreover, the neutrophil respiratory burst was partially suppressed by prostaglandin E2 (PGE2) and the phosphodiesterase type IV (PDE-IV) inhibitor RO 20-1724. When salmeterol was used in combination with PGE2 or RO 20-1724, additive inhibitory effects were observed. The inhibitory activity of salmeterol was not reversed in the presence of the β-blocker propranolol, and did not correlate with its ability of increasing cyclic AMP (cAMP) levels. Finally, the compounds used did not affect neutrophil adherence to fibronectin-coated wells. The results suggest that salmeterol is capable of down-regulating the neutrophil oxidative response to fMLP, also of co-operating with PGE2 and PDE-IV inhibitor RO 20-1724 in a manner not related to its β2-receptor binding activity. In other words, salmeterol displays neutrophil-directed effects, susceptible to be amplified by natural mediators such as PGE2 or PDE-IV inhibitors, consistent with possible anti-inflammatory properties of the drug.
Complement plays an essential role in shock following intestinal ischaemia in rats
Authors: Ikai M , Itoh M , Joh T , Yokoyama Y , Okada N , Okada H 
Published: November 2003

Abstract
Intestinal ischaemia lasting more than 30 min in rats causes fatal systemic shock. Systemic shock was suppressed by preadministration of cobra venom factor (CVF), which reduced the serum complement to less than 5% of the normal level, indicating that complement is involved in the syndrome. After complement activation, anaphylatoxins such as C3a and C5a are generated, and their activity is restricted by carboxypeptidases which remove C-terminal arginine from such bioactive peptides. As expected, preadministration of a carboxypeptidase inhibitor enhanced the systemic shock induced by the intestinal ischaemia. However, when the complement level was suppressed by CVF treatment, no fatal systemic shock was induced by the intestinal ischaemia even with preadministration of the carboxypeptidase inhibitor. These results indicate that complement plays a crucial role in systemic shock induced by intestinal ischaemia, and that anaphylatoxins generated by the complement activation should be involved in induction of the shock syndrome.
Expression of functionally active α4β1 integrin by thymic epithelial cells
Authors: Nieto M , Gómez M , Sánchez-Mateos P , Fernández E , Marazuela M , Sacedón R , Varas A , González-Amaro R , Zapata A G , Toribio M L , Sánchez-Madrid F 
Published: November 2003

Abstract
We have investigated the expression and function of the VLA-4 heterodimer α4β1, a member of the β1 integrin subfamily, on human thymic epithelial cells (TEC) derived from cortical epithelium. The expression of the α4 integrin chain was studied in four different cloned TEC lines derived from either  fetal or post-natal human thymus by both flow cytometry and immunoprecipitation techniques with anti-α4 MoAbs. All different cell lines assayed expressed significant levels of α4, as revealed by their reactivity with MoAbs specific for distinct α4 epitopes. The α4 subunit expressed by TEC was associated to β1 but not to β7 chain, and displayed the characteristic 80/70 kD pattern of proteolytic cleavage. The VLA-4 integrin in these cells was constitutively active in terms of adhesiveness to both fibronectin and vascular cell adhesion molecule-1 (VCAM-1). In addition, this heterodimer localized to punctate regions of the cell in the area of contact with the substratum, named point contacts assessed by staining with the anti-β1 activation epitope 15/7 MoAb. According to the cortical origin of the TEC lines expressing VLA-4, human thymus sections stained with different anti-α4 antibodies revealed the presence of cortical, and in smaller numbers medullary epithelial cells bearing α4 integrin. The expression of α4 in the thymus was also found in both adult and fetal rats, in which epithelial cells were also specifically stained. Altogether, our data show that VLA-4 is an additional component of the integrin repertoire of TEC, and suggest that it could have an important role in thymus epithelial cell–thymocyte interactions.
Blood monocyte activation in rheumatoid arthritis: increased monocyte adhesiveness, integrin expression, and cytokine release
Authors: Lioté F , Boval-Boizard B , Weill D , Kuntz D , Wautier J-L 
Published: November 2003

Abstract
Infiltration of the synovium by mononuclear cells, namely lymphocytes and monocytes, is one of the main features of rheumatoid arthritis (RA) and is considered to be responsible for the development of the disease. In this study in 31 consecutive patients with RA, we investigated whether peripheral blood monocytes exhibited markers of cellular activation related to cell migration. Using flow cytometry with the respective specific antibodies, we studied the expression of integrins CD11a, CD11b, CD11c, CD49d (VLA-4), and CD49e (VLA-5) on monocytes from patients with RA and from normal (N) subjects. IL-1β, IL-6, and tumour necrosis factor-alpha (TNF-α) production by cultured monocytes was measured by immunoassay. Adhesiveness of monocytes was studied on various surfaces (plastic, human fibronectin, gelatin-coated plasma, subendothelial matrix) and on cultured endothelial cells under basal conditions or after stimulation by IL-1β. An increased number of CD14+ monocytes (Mo) from RA patients expressed the CD11b molecule (RA Mo = 90.3%, N Mo = 83.4%, P &lt; 0.005). The expression of CD11b on CD14+ monocytes was significantly increased in RA patients (median fluorescence intensity (FI): RA Mo = 145 (range 80–466) units; normal Mo = 95 (range 24–164) units; P &lt; 0.003). Production of extracellular IL-1β and IL-6 by RA monocytes was significantly enhanced compared with monocytes from normal subjects (IL-1β : RA = 2.65 ± 0.91 ng/ml versusN = 1.35 ± 0.85 pg/ml, P &lt; 0.05; IL-6: RA = 4.83 ± 0.90 ng/ml versusN = 2.40 ± 0.95 ng/ml, P &lt; 0.05). Compared with normal monocytes, RA monocytes exhibited increased adhesion to the various surfaces studied (plastic, P &lt; 0.01; fibronectin, P &lt; 0.01; and gelatin-coated normal or RA plasma, P &lt; 0.01) as well as to unstimulated (P &lt; 0.01) and IL-1β-stimulated endothelial cells (IL-1β for 4 h, P &lt; 0.05; IL-1β for 24 h, P &lt; 0.05). In our study, blood monocytes from RA patients exhibited features of activation related to cell adhesion.
Spontaneous CD30 mRNA expression in peripheral blood mononuclear cells from atopic patients with high IgE serum levels
Authors: Esnault S , Benbernou N , Lavaud F , Guenounou M 
Published: November 2003

Abstract
CD30 is a surface molecule which can be expressed by normal B and T lymphocytes. Our study focused on the CD30 expression and release compared with IL-4 expression as well as CD23-α/β in peripheral blood mononuclear cells (PBMC) from atopic subjects and controls. Data showed a lack of CD30 mRNA expression in the PBMC of control subjects, while it was significantly expressed in those of 6/11 atopic patients. No substantial amounts of spontaneous soluble CD30 (sCD30) could be detected by ELISA in both atopic and control groups. Interestingly, CD30 mRNA expression in PBMC of allergic patients was positively correlated with IgE serum levels (r = 0.79, P = 0.003). Studies on purified B cells showed that CD30 was expressed mainly in CD19+B cells of allergic patients. These data suggest highly a potential functional significance of the CD30 molecule in IgE response during allergic diseases.
Heat shock-enhanced T cell apoptosis with heat shock protein 70 on T cell surface in multicentric Castleman's disease
Authors: Ishiyama T , Koike M , Akimoto Y , Fukuchi K , Watanabe K , Yoshida M , Wakabayashi Y , Tsuruoka N 
Published: November 2003

Abstract
We report here that T cells from patients with multicentric Castleman's disease (MCD) are sensitive to hyperthermia. T cells from two of three patients with MCD revealed DNA ladder formation and chromatin condensation following heat shock (30 min at 41.5°C). Peripheral blood mononuclear cells (PBMC) from the same MCD patients exhibited high levels of spontaneous apoptosis after 72 h in culture and elevated apoptosis after heat shock, as evaluated by a quantitative flow cytometric assay. Heat shock protein 70 (hsp70) was detected on the cell surface of T cells in all three patients after heat shock. Furthermore, hsp70 was detected on T cells in the two MCD patients with apoptosis even in the absence of heat shock. T cells from normal samples did not show either heat-shock-induced expression of cell-surface hsp70 or apoptosis. Thus, heat shock treatment augmented hsp70 expression on the cell surface of T cells and enhanced apoptosis. Our studies suggest that hyperthermia may influence the clinical course of MCD.
Macrophage-colony stimulating factor (M-CSF) enhances proteinuria and recruitment of macrophages into the glomerulus in experimental murine nephritis
Authors: Utsunomiya Y , Omura K , Yokoo T , Imasawa T , Kawamura T , Abe A , Hirano K , Mitarai T , Maruyama N , Sakai O 
Published: November 2003

Abstract
In this study, we examined the effects of macrophage-colony stimulating factor (M-CSF) on glomerular macrophages in lipopolysaccharide (LPS)-induced murine nephritis. Mice injected intraperitoneally with either M-CSF plus LPS, LPS alone, M-CSF alone or saline every day for 8 days were examined for the degree of urine albumin excretion and lymphocyte-function associated antigen-1-positive (LFA-1+) cells in peripheral blood as well as renal pathology. From our results, LPS or M-CSF combined with LPS emphasized the degree of proteinuria, glomerular deposition of immunoglobulins and mesangial proliferation, associated with accumulation of macrophages in the glomeruli. However, in immunohistological examination of kidneys from these nephritic mice, neither intercellular adhesion molecule-1 (ICAM-1), which may play an important role in the recruitment of macrophages into glomeruli, M-CSF receptor nor the number of LFA-1+ cells in peripheral blood was enhanced by M-CSF. On the other hand, M-CSF alone induced neither proteinuria nor any pathological changes and did not increase the number of glomerular Mac-1+ cells above that in saline-treated controls. These results indicate that M-CSF does not directly cause glomerulonephritis but might participate in accelerating the glomerular inflammatory process by stimulating a potent chemoattractant to recruit monocytes-macrophages into the glomeruli.
Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells
Authors: Kanda N , Tsuchida T , Tamaki K 
Published: November 2003

Abstract
We studied the in vitro effect of testosterone on spontaneous immunoglobulin production by human peripheral blood mononuclear cells (PBMC). Testosterone inhibited IgG and IgM production by PBMC both from males and females. The inhibitory effect of testosterone was revealed at doses more than 1 nm, increased dose-dependently, and reached a plateau at 100 nm. At doses &lt;1000 nm, testosterone did not reduce cell viability. Testosterone treatment reduced IgG production by 59.0% and that of IgM by 61.3% compared with control. Immunoglobulin production by B cells was also suppressed by testosterone, though the magnitude of the suppressive effect on B cells was lower than that on whole PBMC; testosterone-induced decrease of IgG production compared with control was 26.9% and that of IgM was 24.9%. Exogenous IL-6 partially restored the impaired immunoglobulin production of testosterone-treated PBMC; IgG production in testosterone culture was increased by IL-6 from 35.6% to 66.5% of control and that of IgM was also increased from 38.9% to 71.2%, respectively. Testosterone treatment reduced IL-6 production of monocytes by 78.4% compared with control, but neither affected that of T cells or B cells. These results suggest that testosterone may suppress immunoglobulin production of human PBMC directly by inhibiting B cell activity and indirectly by reducing IL-6 production of monocytes. It is thus indicated that this hormone may have protective and therapeutic effects on human autoimmune diseases.
Neutrophils in mucosal secretion are functionally active
Authors: Ebenfelt A , Lundqvist H , Dahlgren C , Lundberg C 
Published: November 2003

Abstract
The leucocytes in the secretion on the tonsillar surface have been regarded as inactivated and dying cells with no essential function in the defence of the underlying mucosa. In recent studies, we showed that in acute tonsillitis there are very few, if any, bacteria in the parenchyma, whereas in the secretion on the tonsillar surface there are huge numbers of bacteria and neutrophils, and furthermore, extensive phagocytosis. The present study was performed to elucidate the functional capacity of the neutrophils in the secretion on the tonsillar surface. Secretion samples were taken from the tonsillar surface of healthy volunteers with an imprint technique which allows transfer of secretion from the mucosa to a glass slide with maintained topographic position of the cells. The capacity of the neutrophils to respond to chemotactic stimuli and to phagocytize and further process labelled yeast particles was studied in this in vitro system. The results show that the neutrophils in the secretion have the same properties as in tissue, and also when having arrived in the secretion they can identify and attack new prey.
Differential clearance of glycoforms of IgG in normal and autoimmune-prone mice
Authors: Newkirk M M , Novick J , Stevenson M M , Fournier M-J , Apostolakos P 
Published: November 2003

Abstract
In order to understand better the origins of the elevated levels of the glycoform of IgG that lacks galactose on both arms of the oligosaccharide chain (G0%) located in the Fc, which occurs in man and mouse with age, and in particular in autoimmune disease, we investigated the clearance of two glycosylated forms of IgG2a and IgG1 in normal (BALB/c) and autoimmune-prone (MRL/lpr, MRL/+, and non-obese diabetic (NOD)) mice. To investigate the possibility of different rates of catabolism, enzymatically generated glycoforms of monomeric IgG1 and IgG2a (fully glycosylated or G0%), were iodinated and injected into the tail vein of the mice. We found that the G0% IgG2a remained in circulation significantly longer than the fully glycosylated variants, in all of the mouse strains tested. In contrast, the two forms of IgG1 had similar kinetics in all the autoimmune-prone mice, whereas in BALB/c, there was a longer half-life (t1/2) for G0% IgG1. These data suggest that there may be differences in the ability of the IgG glycoforms to bind to the Fcγ receptors, in particular FcγRI. The clearance rates were found to vary among the strains studied, with MRL/lpr having the fastest catabolic rates for all glycoforms and IgG subclasses tested. This appeared to be due to the presence of circulating IgG and IgM rheumatoid factors (RF). There were significantly increased frequencies and titres for both IgM and IgG RF in MRL/lpr mice compared with the other strains. In contrast, interferon-gamma, known to induce the FcγRI, was found to be similar in the sera, in all of the strains of mice examined. These results suggest that RF probably play an important biological function in the MRL/lpr mice and aid in the clearance of circulating IgG. Our study shows that the state of glycosylation of IgG affects the t1/2in vivo, and that by removing the terminal sugars (sialic acid and galactose), the antibody (IgG2a) will remain in circulation significantly longer. These observations may thus provide a partial explanation for the increase in relative percentage of this glycoform that occurs with age.
Immunogenicity of HIV-1LAI gp160 and env peptides in squirrel monkey Saimiri sciureus using alumine and experimental adjuvants
Authors: Perraut R , Chouteau P , Moog C , Bonnemains B , Kieny M P 
Published: November 2003

Abstract
Since the identification of the HIV virus, important advances have been achieved in the definition of potential subunit vaccines. We investigated the immunogenicity of a recombinant gp160 antigen and of two gp41 peptides from HIV-1LAI associated with seven different adjuvant formulations in squirrel monkeys. All animals were immunized twice with gp160 and then with a gp41 peptide using the same formulation. All adjuvants used led to a subsequent antibody response against gp160, and 55% of the animals immunized developed anti-gp160 antibodies that could neutralize the virus in vitro. Specific anti-gp41 antibody response was also observed. Results obtained underlined the key role of the adjuvant formulation in the antibody response against a given part of the immunogen, and indicate that such immunogenicity-related investigation can be carried out conveniently in the squirrel monkey Saimiri sciureus.
RNA-labelled Ro and La ribonucleoprotein complexes reassembled in vitro; characterization by gel shift analysis
Authors: Granger D , Gendron M , Tremblay A , Chabot B , Ménard H A , Boire G 
Published: November 2003

Abstract
Ro and La RNP complexes were reassembled from in vitro labelled hY5 RNA and HeLa cell extracts. These complexes were then visualized through retardation of migration of labelled hY5 RNA in non-denaturing polyacrylamide gels. Three major complexes (named A, B, and C) were formed when crude cellular extracts (S100 fraction) were used. Using monospecific anti-60-kD Ro (Ro60) and anti-La antibodies to retard RNPs containing these antigens during migration in the gels, the three major complexes were shown to contain Ro60 (C), La (B), or both proteins (A). The specificity of RNA–protein interactions in the reassembled complexes was further demonstrated using two 3′-shortened hY5 RNA transcripts lacking the La-binding site (hY5–Alu I RNA) and both the Ro60 and La-binding sites (hY5–Hha I RNA). hY5–Hha I RNA still formed a single, minor complex when incubated with S100 extract, suggesting interaction with a yet undefined protein. In addition, we used the capacity of specific antibodies to retard the migration of the ressembled complexes to design a detection assay for anti-Ro and anti-La autoantibodies. Using 84 human sera, our assay was shown to approximate the specificity and sensitivity of an immunoprecipitation assay where 32P-labelled cell extracts are used as source of antigens. Our assay may be used to detect low levels of antibodies to conformational determinants on Ro60 and La proteins in human sera and antibody preparations.
Antibody reactivity profiles following immunization with diverse peptides of the PERB11 (MIC) family
Authors: Leelayuwat C , Hollingsworth P , Pummer S , Lertmemongkolchai G , Thom G , Mullberg J , Witt C , Kaufman J , Degli-Esposti M A , Cosman D , Dawkins R 
Published: November 2003

Abstract
PERB11 (MIC) is a gene family possessing multiple copies located within the MHC. Structurally, PERB11 is related to the MHC class I, neonatal IgG Fc receptor (FcRn) and Zn-α2-glycoprotein molecules. The MHC class I family is complex in terms of its genomic arrangement, expression and function, and available evidence suggests that the PERB11 family may be similarly complex. We have adopted an approach to study the expression of such complex gene families by immunizing with multiple peptides and by screening the resulting antibodies against a large range of tissues. The amino acid sequences of PERB11.1 and PERB11.2 as well as those of other related molecules were analysed and compared. Peptides were chosen for immunization based upon (i) loop formation within the equivalent known structure of the MHC class I molecules; (ii) immunogenicity by computer analysis; and (iii) evolutionary relationships. Antibodies in serum from immunized rabbits bound to three out of six peptides used for immunization. ELISA and immunoprecipitation demonstrated binding both to the peptides and to the PERB11.2 recombinant protein. By immunofluorescent staining of various tissues of several species, the three antisera generated overlapping profiles of activity. These included reactions with kidney, small and large intestine, oesophagus, testis, ovary and human neutrophils. This is the first description of antibodies induced by the PERB11 peptides. The extreme complexity of these profiles requires further investigation, but may be explained in terms of antibodies against diverse products of the PERB11 gene family and/or related molecules.