bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of complement activation by recombinant Sh‐CRIT‐ed1 analogues
Authors: Oh Kwang‐Seok , Kweon Mee‐Hyang , Rhee Ki‐Hyeong , Ho Lee Keyong , Sung Ha‐Chin 
Published: August 2003

SummarySh‐CRIT‐ed1 is a potent anti‐complement peptide that inhibits the classical complement‐activation pathway by interfering with the formation of the C3‐convertase complex, C4b2a. C2 is an essential serum glycoprotein that provides the catalytic subunit of the C3 and C5 convertases of the classical pathways of complement activation. Because only in its C4‐bound state is C2a capable of cleaving its physiological protein substrates C3 and C5, the interaction of Sh‐CRIT‐ed1 with C2 plays a decisive role of inhibition in the classical complement‐activation process. However, the role of individual Sh‐CRIT‐ed1 amino acid residues in C2 binding is not fully understood. We constructed nine recombinant Sh‐CRIT‐ed1 (rSh1) analogues, substituted at conserved residues, and evaluated their anti‐complement and C2‐binding activities. Results from glutathione S‐transferase (GST) pull‐down and haemolytic assays suggested that residues 10K, 17E, 19K and 26Y are critical for the interaction of rSh1 with C2. We then constructed an improved anti‐complement peptide by duplicating Sh‐CRIT‐ed1 C‐terminal motifs (17H–26Y). This linear homodimer (rH17d) was more potent than rSh1 with respect to binding to C2 and anti‐complement activity (the 50% inhibitory concentration value was ≈1·2 µm versus ≈6·02 µm for rSh1). Furthermore, rH17d showed higher anti‐complement activity in vivo, providing additional evidence that this duplication is a more effective inhibitor of complement activation than rSh1. Taken together, these results identify four key residues in rSh1 and strongly suggest that rH17d is a potent inhibitor of complement activation that may have therapeutic applications.
Inhibition of DC‐SIGN‐mediated trans infection of T cells by mannose‐binding lectin
Authors: Spear Gregory T. , Zariffard M. Reza , Xin Ji , Saifuddin Mohammed 
Published: August 2003

SummarySome dendritic cells (DC) express a cell‐surface lectin called ‘dendritic cell‐specific intracellular adhesion molecule 3 (ICAM‐3)‐grabbing non‐integrin’ (DC‐SIGN). DC‐SIGN has been shown to mediate a type of infection called ‘trans’ infection, where DC bind human immunodeficiency virus (HIV) and efficiently transfer the virus to T cells. We investigated the possibility that mannose‐binding lectin (MBL), a soluble lectin that functions as a recognition molecule in innate immunity and that binds to HIV, could block trans infection mediated by DC‐SIGN. Binding studies with glycoprotein (gp)120/gp41‐positive and ‐negative virus preparations suggested that DC‐SIGN and MBL bind primarily to glycans on gp120/gp41, as opposed to glycans on host‐cell‐derived proteins, indicating a close overlap in the binding site of the two lectins and supporting the notion that MBL could prevent binding of HIV to DC‐SIGN. Preincubation of X4, R5 or dual‐tropic HIV strains with MBL prevented DC‐SIGN‐mediated trans infection of T cells. The mechanism of MBL blocking trans infection of T cells was at least partly caused by blocking of virus binding to DC‐SIGN positive cells. This study shows that MBL prevents DC‐SIGN‐mediated trans infection of T cells in vitro and suggests that in infected persons, MBL may inhibit DC‐SIGN‐mediated uptake and spread of HIV.
Unimpaired dendritic cell functions in MVP/LRP knockout mice
Authors: Mossink Marieke H. , De Groot Jan , Van Zon Arend , Fränzel‐Luiten Erna , Schoester Martijn , Scheffer George L. , Sonneveld Pieter , Scheper Rik J. , Wiemer Erik A. C. 
Published: August 2003

SummaryDendritic cells (DCs) act as mobile sentinels of the immune system. By stimulating T lymphocytes, DCs are pivotal for the initiation of both T‐ and B‐cell‐mediated immune responses. Recently, ribonucleoprotein particles (vaults) were found to be involved in the development and/or function of human DCs. To further investigate the role of vaults in DCs, we examined the effects of disruption of the major vault protein (MVP/LRP) on the development and antigen‐presenting capacity of DCs, using our MVP/LRP knockout mouse model. Mononuclear bone marrow cells were isolated from wild‐type and knockout mice and stimulated to differentiate to DCs. Like human DCs, the wild‐type murine DC cultures strongly expressed MVP/LRP. Nevertheless, the MVP/LRP‐deficient DCs developed normally and showed similar expression levels of several DC surface markers. No differences were observed in in vitro studies on the antigen uptake and presenting capacities of the wild‐type and MVP/LRP knockout DCs. Moreover, immunization of the MVP/LRP‐deficient mice with several T‐cell antigens led to responses similar to those observed in the wild‐type mice, indicating that the in vivo DC migration and antigen‐presentation capacities are intact. Moreover, no differences were observed in the induction of the T cell‐dependent humoral responses and orally induced peripheral T‐cell tolerance. In conclusion, vaults are not required for primary DC functions. Their abundance in DCs may, however, still reflect basic roles in myeloid cell proliferation and DC development.
Cell activation by monosaccharide lipid A analogues utilizing Toll‐like receptor 4
Authors: Tamai Riyoko , Asai Yasuyuki , Hashimoto Masahito , Fukase Koichi , Kusumoto Shoichi , Ishida Hideharu , Kiso Makoto , Ogawa Tomohiko 
Published: August 2003

SummaryLipid A is the bioactive centre of lipopolysaccharide (LPS), and its properties exhibit various endotoxic and biological effects toward host cells. We examined whether Toll‐like receptors (TLRs) are mediated by the signals from various synthetic acylated derivatives of d‐glucosamine monophosphate. All test synthetic monosaccharide lipid A analogues similar to acylated β‐(1‐6)‐d‐glucosamine disaccharide bisphosphates, such as Escherichia coli‐type lipid A (compound 506) and its precursor (compound 406), clearly induced nuclear factor (NF)‐κB activation in Ba/F3 cells expressing murine TLR4 and its accessory protein MD‐2 (Ba/mTLR4/mMD‐2), but no induction was found in those expressing murine TLR2 (Ba/mTLR2). Compound 411, the non‐reducing sugar moiety of compound 506, exhibited interleukin‐8 (IL‐8) and tumour necrosis factor‐α (TNF‐α)‐producing activities in human peripheral blood mononuclear cells (PBMC), whereas compound 401, the reducing moiety of compounds 506 and 406, and Gifu lipid A‐46 (GLA‐46), the non‐reducing moiety of compound 406, induced no production of IL‐8 and TNF‐α, which was similar to the findings for compound 406. Among the synthetic triacylated monosaccharide lipid A analogues, some compounds with three tetradecanoyl (C14) groups or that included a dodecanoyl (C12) group were more active toward murine and human cells than were other analogues with a decanoyl (C10) or hexadecanoyl (C16) group. Furthermore, IL‐8 production in PBMC stimulated with the active monosaccharide lipid A analogues as well as compound 506 was clearly inhibited by the monoclonal antibody to human TLR4. These findings suggest that monosaccharide lipid A analogues similar to disaccharide lipid As are capable of activating both murine and human cells through TLR4.
The Bcl‐2 family pro‐apoptotic molecule, BNIP3 regulates activation‐induced cell death of effector cytotoxic T lymphocytes
Authors: Wan J. , Martinvalet D. , Ji X. , Lois C. , Kaech S. M. , Von Andrian U. H. , Lieberman J. , Ahmed R. , Manjunath N. 
Published: August 2003

SummaryBNIP3 is a recently described pro‐apoptotic member of the Bcl‐2 family and in BNIP3 cDNA‐transfected cell lines, cell death occurs via a caspase‐independent pathway with opening of the mitochondrial permeability transition (PT) pore and rapid loss of mitochondrial transmembrane potential (Δψm). However, its expression or function in physiologic cell types is not known. Our results using the T‐cell receptor transgenic mice P14, specific for lymphocyte choreomeningitis virus (LCMV) glycoprotein, show that in contrast to the other Bcl‐2 family pro‐apoptotic molecules, BNIP3 is transcriptionally highly up‐regulated in effector cytotoxic T lymphocytes (CTL). Because CTL have a propensity to undergo activation‐induced cell death (AICD) upon restimulation, we tested for other features associated with BNIP3‐induced cell death. AICD of CTL was caspase‐independent as determined by measuring caspase activation during target cell killing as well as by lack of inhibition with caspase inhibitors. Moreover, similar to BNIP3‐induced cell death, CTL apoptosis was associated with increased production of reactive oxygen species and decreased Δψm. Finally, retroviral transduction of BNIP3 antisense RNA diminished AICD in effector CTL. These results suggest that BNIP3 may play an important role in T‐cell homeostasis by regulating effector CTL numbers.
Enhanced mucosal and systemic immune responses to Helicobacter pylori antigens through mucosal priming followed by systemic boosting immunizations
Authors: Vajdy Michael , Singh Manmohan , Ugozzoli Mildred , Briones Maylene , Soenawan Elawati , Cuadra Lina , Kazzaz Jina , Ruggiero Paolo , Peppoloni Samuele , Norelli Francesco , Del Giudice Giuseppe , O'Hagan Derek 
Published: August 2003

Summary It is estimated that Helicobacter pylori infects the stomachs of over 50% of the world's population and if not treated may cause chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and gastric B‐cell lymphoma. The aim of this study was to enhance the mucosal and systemic immune responses against the H. pylori antigens cytotoxin‐associated gene A (CagA) and neutrophil‐activating protein (NAP), through combinations of mucosal and systemic immunizations in female BALB/c mice. We found that oral or intranasal (i.n.) followed by i.m. immunizations induced significantly higher serum titres against NAP and CagA compared to i.n. alone, oral alone, i.m. alone, i.m. followed by i.n. or i.m. followed by oral immunizations. However, only oral followed by i.m. immunizations induced anti‐NAP antibody‐secreting cells in the stomach. Moreover, mucosal immunizations alone or in combination with i.m., but not i.m. immunizations alone, induced mucosal immunoglobulin A (IgA) responses in faeces. Any single route or combination of immunization routes with NAP and CagA preferentially induced antigen‐specific splenic interleukin‐4‐secreting cells and far fewer interferon‐γ‐secreting cells in the spleen. Moreover, i.n. immunizations alone or in combination with i.m. immunizations induced predominantly serum IgG1 and far less serum IgG2a. Importantly, we found that while both i.n. and i.m. recall immunizations induced similar levels of serum antibody responses, mucosal IgA responses in faeces were only achieved through i.n. recall immunization. Collectively, our data show that mucosal followed by systemic immunization significantly enhanced local and systemic immune responses and that i.n. recall immunization is required to induce both mucosal and systemic memory type responses.
Differences in cytokine synthesis by the sub‐populations of dendritic cells from afferent lymph
Authors: Stephens Sue A. , Brownlie Joe , Charleston Bryan , Howard Chris J. 
Published: August 2003

SummaryTwo phenotypically distinct subpopulations of dendritic cells (SIRPα+ CC81Ag− DC and SIRPα− CC81Ag+ DC) have previously been identified in bovine afferent lymph which show functional differences when assayed in vitro. The purpose of this study was to investigate whether differences in cytokine production between the two subpopulations might occur which could influence the bias of the immune response they stimulate. Qualitative and quantitative polymerase chain reactions were used to detect specific mRNA transcripts and flow cytometry and enzyme‐linked immunosorbent assays were used to detect protein production. The SIRPα− CC81Ag+ DC produced considerably more interleukin‐12 (IL‐12) mRNA transcripts and protein than the SIRPα+ CC81Ag− DC. Conversely, SIRPα+ CC81Ag− DC contained more of both transcripts and protein for IL‐1 and of transcripts for IL‐6. A small percentage of both subpopulations produced interferon‐γ (IFN‐γ) as evidenced by cytoplasmic staining. Stimulation of DC by culture with CD40L+ cells increased the production of IL‐1, IL‐6 and IL‐12 but quantitative differences between the subpopulations remained. Production of IL‐10 was also evident following culture with CD40L+ cells or lipopolysaccharide primarily by the SIRPα+ CC81Ag− DC. No evidence was found for type 1 IFN production, and hence plasmacytoid DC, by DC in afferent lymph; both subpopulations appear to be myeloid in origin. These different cytokine repertoires of the two subpopulations of ex vivo DC isolated from afferent lymph imply functional differences that could influence the presentation of antigen to T cells and bias of the immune response following vaccination or infection.
Arginase and autoimmune inflammation in the central nervous system
Authors: Xu Lingyun , Hilliard Brendan , Carmody Ruaidhrí J. , Tsabary Galit , Shin Hyunshun , Christianson David W. , Chen Youhai H. 
Published: August 2003

SummaryUsing a high throughput gene microarray technology that detects ∼22 000 genes, we found that arginase I was the most significantly up‐regulated gene in the murine spinal cord during experimental autoimmune encephalomyelitis (EAE). By Northern blot and arginase enzyme assay, we detected high levels of arginase I mRNA and protein, respectively, in the spinal cord of EAE mice, but not in the spinal cord of normal mice or mice that had recovered from EAE. In vitro, both microglia and astrocytes produced arginase and nitric oxide synthase, two enzymes that are involved in arginine metabolism. To explore the roles of arginase in EAE, we injected the arginase inhibitor amino‐6‐boronohexanoic acid (ABH) into mice during the inductive and effector phases of the disease. Compared with mice that received vehicle control, mice treated with ABH developed milder EAE with delayed onset, reduced disease score and expedited recovery. Spleen mononuclear cells from ABH‐treated mice produced more nitric oxide and secreted less interferon‐γ and tumour necrosis factor‐α as compared to control mice. These results indicate that arginase plays important roles in autoimmune inflammation in the central nervous system.
Allograft inflammatory factor‐1 regulates trinitrobenzene sulphonic acid‐induced colitis
Authors: Morohashi Taiki , Iwabuchi Kazuya , Watano Keiko , Dashtsoodol Nyambayar , Mishima Tetsuya , Nakai Yukihito , Shimada Shigeki , Nishida Ryutaro , Fujii Satoshi , Onoé Kazunori 
Published: August 2003

Summary The expression of allograft inflammatory factor‐1 (AIF‐1) in 2,4,6‐trinitrobenzene sulphonic acid (TNBS)‐induced colitis, a model for T helper 1 (Th1) type disease, was investigated in BALB/c mice. The AIF‐1 expression was significantly increased in the colitis lesion compared to that in the normal colon. We then prepared AIF‐1 transgenic mice (Tgm) with the BALB/c background that express high levels of AIF‐1 in lymphoid tissues and the colon. When AIF‐1 Tgm were administrated TNBS, the TNBS‐induced colitis was ameliorated compared with that in non‐transgenic littermates. The amelioration of colitis was associated with the low expression of interleukin‐1β in the colon. The present findings suggest that AIF‐1 regulates Th1‐type inflammatory responses.
RETRACTED: 5‐lipoxygenase knockout mice exhibit a resistance to acute pancreatitis induced by cerulein
Authors: Cuzzocrea Salvatore , Rossi Antonietta , Serraino Ivana , Di Paola Rosanna , Dugo Laura , Genovese Tiziana , Britti Domenico , Sciarra Giuseppe , De Sarro Angelina , Caputi Achille P. , Sautebin Lidia 
Published: August 2003

SummaryHere we compare the degree of pancreatitis caused by cerulein in mice lacking 5‐lipoxygenase (5‐LO) and in the corresponding wild‐type mice. Intraperitoneal injection of cerulein in mice resulted in severe, acute pancreatitis characterized by oedema, neutrophil infiltration and necrosis and elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for intracellular adhesion molecule‐1 (ICAM‐1), P‐selectin and E‐selectin in the pancreas and lung of cerulein‐treated mice. In contrast, the degree of (1) pancreatic inflammation and tissue injury (histological score), (2) up‐regulation/expression of P‐selectin, E‐selectin and ICAM‐1, and (3) neutrophil infiltration was markedly reduced in pancreatic and lung tissue obtained from cerulein‐treated 5‐LO‐deficient mice. These findings support the view that 5‐LO plays an important, pro‐inflammatory role in the acute pancreatitis caused by cerulein in mice.
Potential role of soluble CD40 in the humoral immune response impairment of uraemic patients
Authors: Contin Cécile , Pitard Vincent , Delmas Yahsou , Pelletier Nadège , Defrance Thierry , Moreau Jean‐François , Merville Pierre , Déchanet‐Merville Julie 
Published: August 2003

SummaryCD40/CD154 interaction is essential for both humoral and cellular immune response. We investigated whether this interaction could be altered in patients with kidney failure who are known to present an impaired immune response. To that aim, we measured the levels of the soluble form of CD40 (sCD40), which is known to interfere with CD40/CD154 interaction, in 43 chronic renal failure patients, 162 hemodialysed patients, and 83 healthy donors. Uraemic and haemodialysed patients presented a three‐ and fivefold increase, respectively, of the antagonist soluble form of CD40 in their serum, when compared to healthy subjects. Serum sCD40 levels correlated with those of creatinine in uraemic non‐haemodialysed patients. While sCD40 is widely excreted in urine of healthy individuals, it is not eliminated by dialysis sessions on classic membranes. The return to a normal kidney function in nine haemodialysed patients who received renal transplantation, leads to a rapid decrease of serum sCD40 levels. This natural sCD40 exhibited multimeric forms and was able to inhibit immunoglobulin production by CD154‐activated B lymphocytes in vitro. Furthermore, the positive correlation we observed between the serum levels of sCD40 and the deficient response to hepatitis B vaccination in uraemic patients suggests that sCD40 also compromises the humoral response in vivo.
Facets of heat shock protein 70 show immunotherapeutic potential
Authors: Todryk Stephen M. , Gough Michael J. , Pockley A. Graham 
Published: August 2003

SummaryAmongst the families of intracellular molecules that chaperone and assist with the trafficking of other proteins, notably during conditions of cellular stress, heat shock protein (hsp) 70 is one of the most studied. Although its name suggests that expression is exclusively induced during cellular hyperthermia, members of the hsp70 family of proteins can be constitutively expressed and/or induced by a range of other cellular insults. The ubiquitous presence of hsp70 in eukaryotic and prokaryotic cells, combined with its high degree of sequence homology and intrinsic immunogenicity, have prompted the suggestion that inappropriate immune reactivity to hsp70 might lead to pro‐inflammatory responses and the development of autoimmune disease. Indeed, hsp70 has been shown to be a potent activator of innate immunity and aberrant expression of hsp70 in certain organs promotes immunopathology. However, studies also suggest that hsp70 might have immunotherapeutic potential, as hsp70 purified from malignant and virally infected cells can transfer and deliver antigenic peptides to antigen‐presenting cells to elicit peptide‐specific immunity and, in contrast to its reported pro‐inflammatory effects, the administration of recombinant hsp70 can attenuate experimental autoimmune disease. This review focuses on the immunoregulatory capacity of hsp70 and its potential therapeutic value.
Heat shock protein derived from a non‐autologous tumour can be used as an anti‐tumour vaccine
Authors: Casey David G. , Lysaght Joanne , James Tharappel , Bateman Andrew , Melcher Alan A. , Todryk Stephen M. 
Published: August 2003

SummaryAntigenic cross‐reactivity between certain tumours has allowed the development of more widely applicable, major histocompatibility complex‐disparate (allogeneic) whole‐cell vaccines. This principle should also allow heat shock proteins (hsp) derived from certain tumours (and carrying cross‐reactive antigens) to be used as vaccines to generate anti‐tumour immunity in a range of cancer patients. Here, hsp70 derived from gp70‐antigen+ B16 melanoma generated cytotoxic‐T‐lymphocyte‐mediated immune protection in BALB/c mice against challenge with gp70‐antigen+ CT26 colorectal tumour cells. Using ovalbumin as a model tumour antigen, it is shown that hsp70 enhances peptide re‐presentation by dendritic cells via class I over equimolar whole ovalbumin antigen. However, while transfection of tumour cells with inducible hsp70 increases hsp yield from tumours, it does not enhance antigen recognition via purified hsp70 nor via whole cells or their lysate.
Effects of fire and spruce beetle outbreak legacies on the disturbance regime of a subalpine forest in Colorado
Authors: Kulakowski Dominik , Veblen Thomas T. , Bebi Peter 
Published: August 2003

AbstractAim There is increasing research attention being given to the role of interactions among natural disturbances in ecosystem processes. We studied the interactions between fire and spruce beetle (Dendroctonus rufipennis Kirkby) disturbances in a Colorado subalpine forest. The central questions of this research were: (1) How does fire history influence stand susceptibility to beetle outbreak? And conversely, (2) How does prior occurrence of a beetle outbreak influence stand susceptibility to subsequent fire?Methods We reconstructed the spatial disturbance history in a c. 4600 ha area by first identifying distinct patches in the landscape on aerial photographs. Then, in the field we determined the disturbance history of each patch by dating stand origin, fire scars, dates of mortality of dead trees, and releases on remnant trees. A geographical information system (GIS) was used to overlay disturbance by fire and spruce beetle.Results and main conclusions  The majority of stands in the study area arose following large, infrequent, severe fires occurring in c. 1700, 1796 and 1880. The study area was also affected by a severe spruce beetle outbreak in the 1940s and a subsequent low‐severity fire. Stands that originated following stand‐replacing fire in the late nineteenth century were less affected by the beetle outbreak than older stands. Following the beetle outbreak, stands less affected by the outbreak were more affected by low‐severity fire than stands more severely affected by the outbreak. The reduced susceptibility to low‐severity fire possibly resulted from increased moisture on the forest floor following beetle outbreak. The landscape mosaic of this subalpine forest was strongly influenced by the interactions between fire and insect disturbances.