bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerated Clearance of Escherichia coli in Experimental Peritonitis of Histamine-Deficient Mice
Authors: Hori Yoshio , Nihei Yoshihiro , Kurokawa Yoshimochi , Kuramasu Atsuo , Makabe-Kobayashi Yoko , Terui Tadashi , Doi Hideyuki , Satomi Susumu , Sakurai Eiko , Nagy Andras , Watanabe Takehiko , Ohtsu Hiroshi 
Published: April 2014

Abstract
We prepared a model of experimental peritonitis by introducing Escherichia coli into the peritoneal cavity of the histamine-deficient mice generated by a disruption of the gene for histidine decarboxylase (HDC), the unique histamine-synthesizing enzyme. When we inoculated E. coli into the peritoneal cavities of the HDC−/− (histamine-deficient) mice, they eliminated E. coli more efficiently than did the wild-type mice. Histamine was released efficiently from the peritoneal cells after E. coli inoculation in HDC+/+ mice, although only trace amounts were detected in the peritoneal cells of HDC−/− mice. Two histamine agonists (6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)hepatanecarboxamide (H1) and dimaprit (H2)) impaired the clearance of E. coli from the peritoneal cavity in HDC−/− mice, suggesting that the activation of both H1 and H2 receptors suppresses the clearance. In contrast, two kinds of H1 and H2 receptor antagonists, cimetidine and pyrilamine, promoted the clearance of E. coli in HDC+/+ mice. Phagocytosis appeared to be enhanced in HDC−/− mice, since the number of neutrophils in the peritoneal cavity of HDC−/− mice was markedly increased. This enhanced recruitment of neutrophils was suppressed in the presence of the histamine agonists, 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)hepatanecarboxamide and dimaprit. In this report histamine was first shown to be an important mediator in an E. coli infectious peritonitis model, causing a delay in the elimination of bacteria. This also raised the possibility of the use of antihistamine drugs for bacterial infection.
Cytomegalovirus Seropositivity Drives the CD8 T Cell Repertoire Toward Greater Clonality in Healthy Elderly Individuals
Authors: Khan Naeem , Shariff Naseer , Cobbold Mark , Bruton Rachel , Ainsworth Jenni A. , Sinclair Alan J. , Nayak Laxman , Moss Paul A. H. 
Published: April 2014

Abstract
The deterioration in immune function with aging is thought to make a major contribution to the increased morbidity and mortality from infectious disease in old age. One aspect of immune senescence is the reduction in CD8 T cell repertoire as due to the accumulation of oligoclonal, memory T cells and a reduction in the naive T cell pool. CD8 T cell clonal expansions accumulate with age, but their antigenic specificity remains unknown. In this study, we show that in elderly individuals seropositivity for human CMV leads to the development of oligoclonal populations of CMV-specific CTL that can constitute up to one-quarter of the total CD8 T cell population. Furthermore, CMV-specific CTL have a highly polarized membrane phenotype that is typical of effector memory cells (CD28−, CD57+, CCR7−). TCR analyses show that CMV-specific CTL have highly restricted clonality with greater restriction in the larger expansions. Clonal analysis of the total CD8 T cell repertoire was compared between CMV-seropositive and CMV-seronegative donors. Thirty-three percent more clonal expansions were observed in CMV-seropositive donors in comparison with seronegative individuals. These data implicate CMV as a major factor in driving oligoclonal expansions in old age. Such a dramatic accumulation of virus-specific effector CTL might impair the ability to respond to heterologous infection and may underlie the negative influence of CMV seropositivity on survival in the very elderly.
Development and Compartmentalization of the Porcine TCR δ Repertoire at Mucosal and Extraintestinal Sites: The Pig as a Model for Analyzing the Effects of Age and Microbial Factors
Authors: Holtmeier Wolfgang , Käller Judith , Geisel Wiebke , Pabst Reinhard , Caspary Wolfgang F. , Rothkötter Hermann J. 
Published: April 2014

Abstract
γδ T cells are an important component of the mucosal immune system. Previously, we have shown that the TCR δ repertoire in human intestine is polyclonal at birth and becomes increasingly restricted with age. In this study, we expand those studies to the pig which allows more extensive experiments including several organs. Tissues from different mucosal sites like the stomach, duodenum, ileum, Peyer’s patches, jejunum, and colon, and also extraintestinal sites like the lung, spleen, thymus and mesenteric lymph nodes, were obtained from conventionally reared pigs aged 2 wk to 5.5 years. In addition, tissues were also obtained from 10-wk-old specified pathogen- and germ-free pigs. TCRDV1-DV5 transcripts were amplified by RT-PCR after which complementarity-determining region 3 spectratyping was performed. Individual bands were excised from the gels and directly sequenced. The intestinal TCR δ repertoire showed increasing restriction with age and was highly oligoclonal in the adult 2- to 5.5-year-old pigs. In old pigs, we observed a striking compartmentalization. Different TCR δ repertoires were present between the lungs and the intestinal mucosa but also within different parts of the gastrointestinal tract. However, occasionally we observed identical TCR δ transcripts in the intestine and the lungs and shared clones could be detected also along the entire gastrointestinal tract. Thus, subsets of γδ T cells are likely to transport immunological information between different compartments of the immune system. Furthermore, these data support the hypothesis that in each mucosal site, different Ags are responsible for selecting and maintaining the γδ TCR over time.
Complement Receptor 3 (CD11b/CD18) Mediates Type I and Type II Phagocytosis During Nonopsonic and Opsonic Phagocytosis, Respectively
Authors: Le Cabec Véronique , Carréno Sébastien , Moisand André , Bordier Christine , Maridonneau-Parini Isabelle 
Published: April 2014

AbstractTwo types of opsonic phagocytosis have been defined depending on the receptor engaged: FcγRs mediate type I phagocytosis of IgG-coated particles; complement receptor 3 (CR3) mediates type II phagocytosis of complement-coated particles. In addition to opsonic phagocytosis, CR3 also mediates nonopsonic phagocytosis of zymosan (Z) and Mycobacterium kansasii through engagement of distinct sites. Using Chinese hamster ovary cells stably expressing human CR3, we studied CR3-mediated ingestion of nonopsonized particles, Z or M. kansasii, compared with opsonized zymosan (OZ). We show that 1) while OZ sinks into cells, Z is engulfed by pseudopodia as visualized by electron microscopy; 2) in contrast to OZ, nonopsonic phagocytosis of Z and M. kansasii depends on Rac and Cdc42 but not on Rho activity; and 3) CR3-mediated phagocytosis of Z depends on the kinase activity of the Src family tyrosine kinase Hck, while OZ internalization does not. Therefore, CR3 mediates type I phagocytosis under nonopsonic conditions and type II under opsonic conditions. This is the first evidence that a single receptor can mediate both types of phagocytosis depending on the ligand used.
Protective Immunosurveillance of the Central Nervous System by Listeria-Specific CD4 and CD8 T Cells in Systemic Listeriosis in the Absence of Intracerebral Listeria
Authors: Kwok Lai-Yu , Miletic Hrvoje , Lütjen Sonja , Soltek Sabine , Deckert Martina , Schlüter Dirk 
Published: April 2014

Abstract
The invasion of the CNS by pathogens poses a major risk for damage of the highly vulnerable brain. The aim of the present study was to analyze immunological mechanisms that may prevent spread of infections to the CNS. Intraperitoneal application of Listeria monocytogenes to mice induced infection of the spleen, whereas pathogens remained absent from the brain. Interestingly, Listeria-specific CD4 and CD8 T cells homed to the brain and persisted intracerebrally for at least 50 days after both primary and secondary infection. CD4 and CD8 T cells resided in the leptomeninges, in the choroid plexus, and, in low numbers, in the brain parenchyma. CD4 and CD8 T cells isolated from the brain early after infection (day 7) were characterized by an activated phenotype with spontaneous IFN-γ production, whereas at a later stage of infection (day 28) restimulation with Listeria-specific peptides was required for the induction of IFN-γ production by CD4 and CD8 T cells. In contrast to splenic T cells, T cells in the brain did not exhibit cytotoxic activity. Adoptively transferred T cells isolated from the brains of Listeria-infected mice reduced the bacterial load in cerebral listeriosis. The frequency of intracerebral Listeria-specific T cells was partially regulated by the time of exposure to Listeria and cross-regulated by CD4 and CD8 T cells. Collectively, these data reveal a novel T cell-mediated pathway of active immunosurveillance of the CNS during bacterial infections.
Reversal of Coccidioidal Anergy In Vitro by Dendritic Cells from Patients with Disseminated Coccidioidomycosis
Authors: Richards John O. , Ampel Neil M. , Lake Douglas F. 
Published: April 2014

Abstract
Coccidioides immitis is a pathogenic, dimorphic fungus found in the southwestern United States and is the causative agent of coccidioidomycosis. Extrathoracic dissemination of coccidioidomycosis is associated with a lack of cellular immunity. Dendritic cells (DCs) have been shown to initiate and modulate cellular immune responses. To determine whether DCs could modulate or initiate the immune response in this disease, monocyte-derived DCs were generated from coccidioidal Ag nonresponsive patients with disseminated coccidioidomycosis and healthy nonimmune individuals. DCs generated from both groups demonstrated phenotypes characteristic of DCs and stimulated strong allogeneic MLR. DCs from patients and healthy nonimmune individuals pulsed with the coccidioidal Ag preparation T27K induced lymphocyte proliferation. Mature DCs were much more efficient than immature DCs in these stimulations. Furthermore, restimulation of T27K-primed PBMC with Ag-pulsed DCs generated a C. immitis-specific cellular immune response in PBMC from patients with disseminated coccidioidomycosis as well as healthy nonimmune individuals. These results show that 1) DCs have the capacity to stimulate specific cellular immune responses from patients with disseminated coccidioidomycosis who are nonresponsive to coccidioidal Ag and healthy nonimmune individuals in vitro; 2) DCs can be used to screen coccidioidal Ags as candidates for human vaccine development; and 3) DC therapy may be useful in the treatment of disseminated coccidioidomycosis.
Roles of Toll-Like Receptors in C-C Chemokine Production by Renal Tubular Epithelial Cells
Authors: Tsuboi Naotake , Yoshikai Yasunobu , Matsuo Seiichi , Kikuchi Takeshi , Iwami Ken-Ichiro , Nagai Yoshiyuki , Takeuchi Osamu , Akira Shizuo , Matsuguchi Tetsuya 
Published: April 2014

Abstract
Pyelonephritis, in which renal tubular epithelial cells are directly exposed to bacterial component, is a major predisposing cause of renal insufficiency. Although previous studies have suggested C-C chemokines are involved in the pathogenesis, the exact source and mechanisms of the chemokine secretion remain ambiguous. In this study, we evaluated the involvement of Toll-like receptors (TLRs) in C-C chemokine production by mouse primary renal tubular epithelial cells (MTECs). MTECs constitutively expressed mRNA for TLR1, 2, 3, 4, and 6, but not for TLR5 or 9. MTECs also expressed MD-2, CD14, myeloid differentiation factor 88, and Toll receptor-IL-1R domain-containing adapter protein/myeloid differentiation factor 88-adapter-like. Synthetic lipid A and lipoprotein induced monocyte chemoattractant protein 1 (MCP-1) and RANTES production in MTECs, which strictly depend on TLR4 and TLR2, respectively. In contrast, MTECs were refractory to CpG-oligodeoxynucleotide in chemokine production, consistently with the absence of TLR9. LPS-mediated MCP-1 and RANTES production in MTECs was abolished by NF-κB inhibition, but unaffected by extracellular signal-regulated kinase inhibition. In LPS-stimulated MTECs, inhibition of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase significantly decreased RANTES, but did not affect MCP-1 mRNA induction. Thus, MTECs have a distinct expression pattern of TLR and secrete C-C chemokines in response to direct stimulation with a set of bacterial components.
A Functional Role for Circulating Mouse L-Selectin in Regulating Leukocyte/Endothelial Cell Interactions In Vivo
Authors: Tu LiLi , Poe Jonathan C. , Kadono Takafumi , Venturi Guglielmo M. , Bullard Daniel C. , Tedder Thomas F. , Steeber Douglas A. 
Published: April 2014

AbstractL-selectin mediates the initial capture and subsequent rolling of leukocytes along inflamed vascular endothelium and mediates lymphocyte migration to peripheral lymphoid tissues. Leukocyte activation induces rapid endoproteolytic cleavage of L-selectin from the cell surface, generating soluble L-selectin (sL-selectin). Because human sL-selectin retains ligand-binding activity in vitro, mouse sL-selectin and its in vivo relevance were characterized. Comparable with humans, sL-selectin was present in adult C57BL/6 mouse sera at ∼1.7 μg/ml. Similar levels of sL-selectin were present in sera from multiple mouse strains, despite their pronounced differences in cell surface L-selectin expression levels. Adhesion molecule-deficient mice prone to spontaneous chronic inflammation and mice suffering from leukemia/lymphoma had 2.5- and 20-fold increased serum sL-selectin levels, respectively. By contrast, serum sL-selectin levels were reduced by 70% in Rag-deficient mice lacking mature lymphocytes. The majority of serum sL-selectin had a molecular mass of 65–75 kDa, consistent with its lymphocyte origin. Slow turnover may explain the relatively high levels of sL-selectin in vivo. The t1/2 of sL-selectin, assessed by transferring sera from wild-type mice into L-selectin-deficient mice and monitoring serum sL-selectin levels by ELISA, was &gt;20 h, and it remained detectable for longer than 1 wk. Short-term in vivo lymphocyte migration assays demonstrated that near physiologic levels (∼0.9 μg/ml) of sL-selectin decreased lymphocyte migration to peripheral lymph nodes by &gt;30%, with dose-dependent inhibition occurring with increasing sL-selectin concentrations. These results suggest that sL-selectin influences lymphocyte migration in vivo and that the increased sL-selectin levels present in certain pathologic conditions may adversely affect leukocyte migration.
Key Role for Mast Cells in Nonatopic Asthma
Authors: Kraneveld Aletta D. , van der Kleij Hanneke P. M. , Kool Mirjam , van Houwelingen Anneke H. , Weitenberg Andrys C. D. , Redegeld Frank A. M. , Nijkamp Frans P. 
Published: April 2014

AbstractThe mechanisms involved in nonatopic asthma are poorly defined. In particular, the importance of mast cells in the development of nonatopic asthma is not clear. In the mouse, pulmonary hypersensitivity reactions induced by skin sensitization with the low-m.w. compound dinitrofluorobenzene (DNFB) followed by an intra-airway application of the hapten have been featured as a model for nonatopic asthma. In present study, we used this model to examine the role of mast cells in the pathogenesis of nonatopic asthma. First, the effect of DNFB sensitization and intra-airway challenge with dinitrobenzene sulfonic acid (DNS) on mast cell activation was monitored during the early phase of the response in BALB/c mice. Second, mast cell-deficient W/Wv and Sl/Sld mice and their respective normal (+/+) littermate mice and mast cell-reconstituted W/Wv mice (bone marrow-derived mast cells→W/Wv) were used. Early phase mast cell activation was found, which was maximal 30 min after DNS challenge in DNFB-sensitized BALB/c, +/+ mice but not in mast cell-deficient mice. An acute bronchoconstriction and increase in vascular permeability accompanied the early phase mast cell activation. BALB/c, +/+ and bone marrow-derived mast cell→W/Wv mice sensitized with DNFB and DNS-challenged exhibited tracheal hyperreactivity 24 and 48 h after the challenge when compared with vehicle-treated mice. Mucosal exudation and infiltration of neutrophils in bronchoalveolar lavage fluid associated the late phase response. Both mast cell-deficient strains failed to show any features of this hypersensitivity response. Our findings show that mast cells play a key role in the regulation of pulmonary hypersensitivity responses in this murine model for nonatopic asthma.
Up-Regulation of Functional Kinin B1 Receptors in Allergic Airway Inflammation
Authors: Christiansen Sandra C. , Eddleston Jane , Woessner Katharine M. , Chambers Sandra S. , Ye Richard , Pan Zhixing K. , Zuraw Bruce L. 
Published: April 2014

Abstract
B1 receptors are known to be induced during allergic airway inflammation in animal models. However, little is known regarding in vivo B1 receptor expression in humans. We examined B1 receptor mRNA expression in nasal tissue samples from allergic rhinitis and normal subjects. Allergic rhinitis subjects displayed significantly higher expression of B1 receptor mRNA than did the normal subjects, and nasal allergen challenge increased B1 receptor mRNA expression at 8 to 24 h time points in allergic rhinitis subjects. No significant difference was found in B2 receptor expression. To confirm B2 and B1 receptor functional activity, subjects were challenged with kinin agonists. Nasal challenge with the B1 receptor ligand, Lys-des-Arg-bradykinin (BK), activated extracellular signal-regulated kinase in allergic rhinitis, but not normal, subjects. Nasal challenge with the B2 receptor ligand, BK, activated extracellular signal-regulated kinase in both allergic rhinitis and normal subjects. The consequences of B1 receptor activation were investigated using the human airway epithelial cell lines A549 and BEAS-2B. We demonstrated that Lys-des-Arg-BK activates the transcription factor AP-1. Taken together, these results show that functional B1 receptors are induced in the airway during allergic inflammation and suggest that they participate in the regulation of gene expression.
IgE-Dependent Mast Cell Activation Potentiates Airway Responses in Murine Asthma Models
Authors: Mayr Susanne I. , Zuberi Riaz I. , Zhang Min , de Sousa-Hitzler Jean , Ngo Karen , Kuwabara Yasuko , Yu Lan , Fung-Leung Wai-Ping , Liu Fu-Tong 
Published: April 2014

AbstractWe have studied murine models of asthma using FcεRIα-chain-deficient (FcεRIα−/−) mice to investigate the role of IgE-dependent mast cell activation in these models. When mice were either 1) immunized once with OVA in alum i.p. and then challenged with OVA intranasally, or 2) repeatedly immunized with OVA in the absence of adjuvant and subsequently challenged with nebulized OVA, FcεRα−/− mice had significantly fewer eosinophils and lower IL-4 levels in their bronchoalveolar lavage fluid compared with wild-type mice. When mice were given anti-IL-5 antibody before OVA challenge in protocol 1, eosinophilic infiltration into the airways was significantly suppressed in both genotypes, but only FcεRIα−/− mice showed significantly reduced airway hyperresponsiveness (AHR). In addition, when mice immunized and challenged with OVA also received a late OVA provocation at a higher concentration and were then exposed to methacholine, only wild-type mice developed a substantial increase in AHR. Since FcεRI is expressed mainly on mast cells in mouse airways, we conclude that IgE-dependent activation of this cell type plays an important role in the development of allergic airway inflammation and AHR in mice. The models used may be of value for testing inhibitors of IgE or mast cells for development of therapeutic agents for human asthma.
Hypoxia Diminishes Toll-Like Receptor 4 Expression Through Reactive Oxygen Species Generated by Mitochondria in Endothelial Cells
Authors: Ishida Itaru , Kubo Hiroshi , Suzuki Satoshi , Suzuki Tomoko , Akashi Sachiko , Inoue Kunihiko , Maeda Sumiko , Kikuchi Hideaki , Sasaki Hidetada , Kondo Takashi 
Published: April 2014

AbstractHypoxia and inflammation often occur simultaneously due to prevention of adequate gas exchange. Understanding the influence of hypoxia on the inflammatory response is important because hypoxia directly regulates expression of many genes, including those regulating inflammation, and plays a role in modulating the resolution of an inflammatory response. LPS is a major mediator of cellular injury and inflammation that induces its effects through Toll-like receptor 4 (TLR4). The aim of this study was to evaluate the effect of hypoxia on TLR4 expression. Hypoxia decreased TLR4 expression on cultured endothelial cells. Furthermore, LPS-induced ICAM-1 up-regulation was decreased by hypoxia. Because reactive oxygen species (ROS) generated from mitochondria are one of the signaling molecules induced by hypoxia, the role of ROS in hypoxia-induced TLR4 down-regulation was evaluated. Our data showed that hypoxia increased ROS generation and that hypoxia-induced TLR4 down-regulation was inhibited by myxothiazol, a mitochondrial site III electron transport inhibitor. Hypoxia also inhibited AP-1 translocation. Since the TLR4 promoter has a binding site for AP-1, hypoxia-induced TLR4 down-regulation may be due to an ROS-mediated decrease in AP-1-binding activity. We conclude that hypoxia decreases TLR4 expression in endothelial cells and that this change is mediated by mitochondrial ROS leading to attenuation of AP-1 transcriptional activity.
Multivalent Metal-Induced Iron Acquisition from Transferrin and Lactoferrin by Myeloid Cells
Authors: Olakanmi Oyebode , Rasmussen George T. , Lewis Troy S. , Stokes John B. , Kemp John D. , Britigan Bradley E. 
Published: April 2014

Abstract
We previously described a unique, high-capacity, ATP-independent mechanism through which myeloid cells acquire Fe from low-m.w. chelates. The rate of this Fe acquisition is markedly increased by cellular exposure to multivalent metal cations. Because most Fe in vivo is bound to transferrin or lactoferrin, we examined whether this mechanism also contributes to myeloid cell acquisition of Fe from transferrin and/or lactoferrin. Using HL-60 cells as a model system, we show cellular acquisition of 59Fe from both lactoferrin and transferrin that was unaffected by conditions that depleted the cells of ATP or disrupted their cytoskeleton. Fe acquisition was dramatically increased by cell exposure to various metals including Ga3+, Gd3+, Al3+, Fe3+, La3+, Zr4+, Sn4+, Cu2+, and Zn2+ by a process that was reversible. Exposure to these same metals also increased binding of both transferrin and lactoferrin to the cell surface by a process that does not appear to involve the well-described plasma membrane receptor for transferrin. Approximately 60% of the Fe acquired by the cells from transferrin and lactoferrin remained cell associated 18 h later. HL-60 cells possess a high-capacity multivalent metal-inducible mechanism for Fe acquisition from transferrin and lactoferrin that bears many similarities to the process previously described that allows these and other cell types to acquire Fe from low-m.w. Fe chelates. The biologic importance of this mechanism may relate to its high Fe acquisition capacity and the speed with which it is able to rapidly adapt to the level of extracellular Fe.