bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parallel induction of epithelial surface-associated chemokine and proteoglycan by cellular hypoxia: implications for neutrophil activation
Authors: Furuta Glenn T , Dzus Andrea L , Taylor Cormac T , Colgan Sean P 
Published: September 2022

Abstract
Neutrophil-induced damage to the protective epithelium has been implicated in mucosal disorders associated with hypoxia, and such damage may be initiated by epithelial-derived chemokines. Because chemokines can bind to membrane proteoglycans, we hypothesized that chemokines may associate with epithelial surfaces and activate polymorphonuclear neutrophils (PMN). Epithelial hypoxia (pO2 20 torr) resulted in a time-dependent induction of interleukin-8 (IL-8) mRNA, soluble protein, as well as surface protein. Such surface IL-8 expression was demonstrated to be dependent on heparinase III expression, and extensions of these experiments indicated that hypoxia induces epithelial perlecan expression in parallel with IL-8. Finally, co-incubation of post-hypoxic epithelia with human PMN induced IL-8-dependent expression of the PMN β2-integrin CD11b/18. These data indicate that chemokines liberated from epithelia may exist in a surface-bound, bioactive form and that hypoxia may regulate proteoglycan expression.
Chronic PMA treatment of Jurkat T lymphocytes results in decreased protein tyrosine phosphorylation and inhibition of CD3- but not Ti-dependent antibody-triggered Ca2+ signaling
Authors: Ahnadi Charaf E , Giguère Patrick , Gravel Serge , Gagné Danièle , Goulet Anne-Christine , Fülöp Tamàs , Payet Marcel D , Dupuis Gilles 
Published: September 2022

Abstract
We have treated Jurkat T lymphocytes with a concentration (160 nM) of phorbol myristyl acetate (PMA) that down-regulates conventional and novel protein kinase C (PKC) isozymes and we have investigated the effects on Ca2+ signaling and protein tyrosine phosphorylation using mAb (C305) directed against the β-subunit of the Ti heterodimer or the ɛ/δ-component of the CD3 complex (mAb Leu 4 or OKT 3). The levels of expression of PKC α, βI, βII, and δ were reduced by 90% or more in PMA-treated cells, whereas the expression of PKCθ decreased by ∼30%. In contrast, the chronic treatment with PMA increased the expression of PKCɛ and PKCζ. There was a lack of Ca2+ response and myo-inositol trisphosphate (IP3) production in PMA-treated cells when they were exposed to mAb Leu 4 but the cells responded to mAb C305. The treatment with PMA did not affect the surface expression of Ti or CD3. The overall levels of tyrosine-phosphorylated proteins were markedly reduced in PMA-treated cells. We investigated whether these observations were related to defects in signal transduction related to protein tyrosine kinase (PTK) of the src and syk families. The electrophoretic mobilities of p59fyn or ZAP-70 were not changed in PMA-treated cells but p56Ick migrated as a large band of Mr 60–62 kDa. The decreased mobility of p56Ick was related to a state of hyperphosphorylation. The activity of modified p56Ick was not up-regulated in activated Jurkat cells. Our data suggest that clonotypic Ti can trigger Ca2+ mobilization independently of conventional PKC isoforms. Our observations further suggest that conventional PKC isoforms are involved early in the cascade of events associated with Jurkat T lymphocyte activation.
Induction of cyclooxygenase-2 expression during HIV-1-infected monocyte-derived macrophage and human brain microvascular endothelial cell interactions
Authors: Pereira Cândida F , Boven Leonie A , Middel Jeena , Verhoef Jan , Nottet Hans S L M 
Published: September 2022

Abstract
Human immunodeficiency virus type-1 (HIV-1)-associated dementia (HAD) is a neurodegenerative disease characterized by HIV infection and replication in brain tissue. HIV-1-infected monocytes overexpress inflammatory molecules that facilitate their entry into the brain. Prostanoids are lipid mediators of inflammation that result from cyclooxygenase-2 (COX-2) activity. Because COX-2 is normally induced during inflammatory processes, the aim of this study was to investigate whether COX-2 expression is up-regulated during monocyte-brain endothelium interactions. In vitro cocultures of HIV-infected macrophages and brain endothelium showed an up-regulation of COX-2 expression by both cell types. This up-regulation occurs via an interleukin-1β (IL-1β)-dependent mechanism in macrophages and via an IL-1β-independent mechanism in endothelial cells. Thus, interactions between HIV-infected monocytes and brain endothelium result in COX-2 expression and, as such, might contribute to the neuropathogenesis of HIV infection.
Primary macrophages infected by human immunodeficiency virus trigger CD95-mediated apoptosis of uninfected astrocytes
Authors: Aquaro Stefano , Panti Stefania , Caroleo Maria Cristina , Balestra Emanuela , Cenci Alessandra , Forbici Federica , Ippolito Giuseppe , Mastino Antonio , Testi Roberto , Mollace Vincenzo , Caliò Raffaele , Perno Carlo Federico 
Published: September 2022

AbstractInfection of macrophages (M/M) by human immunodeficiency virus (HIV) is a main pathogenetic event leading to neuronal dysfunction and death in patients with AIDS dementia complex. Alteration of viability of neurons and astrocytes occurs in vivo even without their infection, thus it is conceivable that HIV-infected M/M may affect viability of such cells even without direct infection. To assess this hypothesis, we studied the effects of HIV-infected M/M on an astrocytic cell-line lacking CD4-receptor expression. Exposure to supernatants of HIV-infected M/M triggers complete disruption and apoptotic death of astrocytic cells. This effect is not related to HIV transmission from infected M/M, because HIV-DNA and p24 production in astrocytic cells remained negative. Apoptotic death of astrocytes is mainly mediated by Fas ligand released in supernatants of HIV-infected M/M (as demonstrated by complete reversal of such phenomenon by adding neutralizing antibodies against CD95 receptor). Treatment of astrocytic cells with recombinant (biologically active) Tat induces &lt;10% apoptosis, and gp120 was totally ineffective. Treatment of HIV-infected M/M with AZT completely reverses the proapoptotic effect of their supernatants on astrocytes, thus demonstrating that productive virus replication within M/M is required for the induction of astrocytic cell death. Taken together, data suggest that homeostasis of astrocytes may be affected by HIV-infected M/M in the absence of productive infection of target cells. This phenomenon may help to explain the cellular damage found in HIV-infected patients also in areas of the brain not strictly adjacent to HIV-infected M/M.
The immunobiology and clinical potential of immunostimulatory CpG oligodeoxynucleotides
Authors: Weiner George J 
Published: September 2022

AbstractOver 100 years ago, Coley first explored the use of bacterial products as immunostimulatory therapy for nonbacterial disease. It is now clear that bacterial DNA, and synthetic oligodeoxynucleotides containing specific motifs centered on a CpG dinucleotide (CpG ODN), are potent immunostimulatory agents. The molecular mechanisms responsible for the immunostimulatory effects of CpG ODN have yet to be elucidated fully, although it is clear that CpG ODN act rapidly on a variety of cell types. This includes activation of B cells, natural killer cells, and antigen-presenting cells including monocytes, macrophages, and dendritic cells. These effects have led to evaluation of CpG ODN as immune adjuvants in immunization where they have been shown in animal models to enhance the development of a TH1-type immune response. Preliminary results from clinical trials using CpG ODN as an immune adjuvant are promising. Preclinical studies suggest CpG ODN can also enhance innate immunity against a variety of infections, synergize with monoclonal antibody to enhance antibody-dependent cellular cytotoxicity, and alter the Th1/Th2 balance as a possible treatment for allergic diseases and asthma. Clinical evaluation has recently begun to determine whether promising preclinical results with CpG ODN can be translated into effective and tolerable clinical treatment approaches.
Functional consequences of FcɛRIα up-regulation by IgE in human basophils
Authors: MacGlashan Donald , Schroeder John T 
Published: September 2022

AbstractThese studies examine the functional changes that occur after up-regulation of FcɛRIα by immunoglobulin E (IgE) for human basophils. Basophils were cultured with and without IgE antibody (PS myeloma IgE or anti-gp120-specific IgE) for 1 week and challenged with anti-IgE, anti-FcɛRIα, or antigen for histamine and IL-4 secretion. There were no statistically significant changes in their response to anti-IgE or anti-receptor antibodies, as compared with controls incubated for the same period, whereas receptor expression increased an average of 4-fold. There was increased responsiveness to antigenic challenge, most notably at suboptimal concentrations of antigen (gp120 peptide-ovalbumin conjugate). For a 6-fold difference in cell surface density of gp120-specific IgE, there was a 2.2-fold change in antigen potency or 3-fold increases in histamine release at lower antigen concentrations. Similar results were found for secretion of IL-4. Basophil sensitivity, which is a measure of the density of antigen-specific IgE required for 50% of maximal secretion, was used to determine whether up-regulation of FcɛRIα was coordinated with up-regulation of other components of the IgE-signaling pathway. The results indicated up-regulation of FcɛRI is not always accompanied by changes that allow sensitivity to be maintained. These results indicate that functional up-regulation does occur but that its magnitude may be modulated because not all components of the signaling pathway are up-regulated in a balanced manner.
Escherichia coli cytotoxic necrotizing factor-1 (CNF-1) increases the adherence to epithelia and the oxidative burst of human polymorphonuclear leukocytes but decreases bacteria phagocytosis
Authors: Hofman Paul , Le Negrate Gaëlle , Mograbi Baharia , Hofman Véronique , Brest Patrick , Alliana-Schmid Annie , Flatau Gilles , Boquet Patrice , Rossi Bernard 
Published: September 2022

Abstract
Recruitment of polymorphonuclear leukocytes (PMNL) is a hallmark of both urinary and digestive infections caused byEscherichia coli. Cytotoxic necrotizing factor 1 (CNF-1) is a toxin produced by uropathogenic E. coli strains that mediates its effects via the activation of small GTP-binding proteins. However, the role and the consequences of CNF-1 on PMNL physiology remain largely unknown. In this study, we provide evidence that CNF-1 dramatically affects the PMNL cytoskeleton architecture by inducing an increased content of F-actin. Furthermore, we demonstrate that CNF-1 increases functional features of PMNL, such as superoxide generation and adherence on epithelial T84 monolayers, but significantly decreases their phagocytic function. Our results suggest that CNF-1 may behave as a virulence factor in urinary or digestive infection by stimulating PMNL cytotoxicity as a result of its enhancing effect on their adherence to epithelial cells as well as the production of radical oxygen products. Moreover, the decreased phagocytosis of PMNL induced by CNF-1 likely facilitates growth of bacteria. In these conditions, CNF-1 would intervene in the initiation and in the perpetuation of the inflammatory process.
Functional heterogeneity of rat hepatic and alveolar macrophages: effects of chronic ethanol administration
Authors: Morio Lisa A , Chiu Hawjyh , Sprowles Karen A , Laskin Debra L 
Published: September 2022

AbstractChronic ethanol consumption is associated with increased incidence of hepatic and pulmonary infections. To determine if this is correlated with altered macrophage activity, we analyzed the functional properties of cells isolated sequentially from the liver and lung of rats fed a liquid diet containing ethanol (35% of calories) or malto-dextrin control for 9–12 weeks. Hepatic and alveolar macrophages from control animals were found to exhibit distinct morphologic and functional properties. Thus, hepatic macrophages were highly vacuolated and appeared larger and more irregular in shape than alveolar macrophages. These cells also displayed greater phagocytic activity and random migration. In contrast, lung macrophages produced more superoxide anion and nitric oxide, and exhibited enhanced chemotactic activity toward the complement fragment C5a. Whereas administration of ethanol to rats for 9–12 weeks resulted in decreased chemotaxis and superoxide anion production by alveolar macrophages, cell adhesion molecule expression was reduced in hepatic macrophages. Nitric oxide production and inducible nitric oxide synthase protein expression were decreased in both macrophage populations. These effects were not observed after 3–6 weeks of ethanol administration to rats. Our results suggest that changes in macrophage functioning may play a role in decreased host defense following chronic ethanol exposure.
Tacrolimus (FK506) treatment of CD34+ hematopoietic progenitor cells promote the development of dendritic cells that drive CD4+ T cells toward Th2 responses
Authors: Shimizu Kanako , Fujii Shin-ichiro , Fujimoto Koji , Kawa Keisei , Yamada Akira , Kawano Fumio 
Published: September 2022

Abstract
The macrolide lactone, tacrolimus (FK506), is utilized in bone marrow transplantation (BMT) to prevent graft-versus-host disease (GVHD). In the current study, we evaluated the ability of FK506 to modify the function of dendritic cells (DCs) derived from CD34+ hematopoietic progenitor cells (HPCs). Comparable to DCs obtained in the absence of FK506, DCs cultured in the presence of FK506 (FK-DCs) had higher expression of CD1a+ and formed a greater number of DC colonies. Despite the same expression of costimulatory molecules, FK-DCs displayed a reduced capacity to stimulate an allogeneic T cell response, and showed significantly lower interleukin (IL)-12 production. While normal DCs pulsed with the exogenous antigen, keyhole limpet hemocyanin (KLH) induced specific Th1-like interferon-γ(IFN-γ) producing CD4+ T cell line, FK-DCs induced Th2-like interleukin-4 (IL-4) producing CD4+ T cell line. These data demonstrate the ability of FK506 to induce Th2-promoting function in developing DCs.
C5a-stimulated human neutrophils use a subset of β2 integrins to support the adhesion-dependent phase of superoxide production
Authors: Tyagi ShivRaj , Klickstein Lloyd B , Nicholson-Weller Anne 
Published: September 2022

Abstract
Isolated human polymorphonuclear neutrophils (PMN) responded to human C5a with an immediate, transient release of superoxide lasting from 0.5 to 5 min. This was followed by a second release of superoxide, which began at 10 min after addition of C5a, was sustained for more than 30 min, and required ICAM-1 immobilized in the wells. F(ab′)2 monoclonal antibody (mAb) preparations were used to dissect the role of individual β2 integrins and to avoid the confounding effects of ligating Fc receptors. Anti-CD18 mAb treatment of the PMN had no effect on the immediate first phase but completely inhibited the second, adhesion-dependent phase of superoxide production. Anti-CR3 mAb only inhibited the adhesion phase of superoxide production partially, implying that other β2 integrins were involved. A mixture of anti-CD11a, anti-CD11b, and anti-CD11c was not able to block superoxide production completely, suggesting a role for αd/β2. Surprisingly, blocking anti-LFA-1 mAb had no effect on superoxide production. Consistent with this observation, immobilized, purified ICAM-2, a specific counter-receptor for LFA-1, did not support the adhesion-dependent phase ofsuperoxide production. Thus, PMN treated with C5a used signals via CR3, P150/95, and αd/β2, but not LFA-1, to support superoxide production. LFA-1 has been shown by others to mediate most of the adhesion necessary for transendothelial migration in vivo. The inability of LFA-1 ligation to stimulate superoxide production may be an important means of preventing blood-vessel damage when PMN migrate across the endothelium.
Differential expression of heat shock protein 70 (hsp70) in human monocytes rendered apoptotic by IL-4 or serum deprivation
Authors: Lang Detlef , Hubrich Andreas , Dohle Frank , Terstesse Martin , Saleh Hilmi , Schmidt Michael , Pauels Hans-Gerd , Heidenreich Stefan 
Published: September 2022

AbstractApoptosis of monocytes is regulated by the balance between pro- and antiapoptotic triggers and pathways and may strongly influence inflammatory disorders. The major heat shock protein, hsp70, is an effective inhibitor of apoptosis in lymphocytic and monocytic tumor cell lines, but the implications in the regulation of apoptosis of freshly isolated human monocytes have not been elucidated. In this study, we examined whether two different triggers of monocyte apoptosis, serum deprivation and IL-4, respectively, altered hsp70 expression and whether expression levels correlated with monocyte survival. Monocyte apoptosis was determined quantitatively by flow cytometry detecting annexin V binding or nuclear stainability with propidium iodide (PI). Hsp70 expression was analyzed by semiquantitative RT-PCR and immunoblotting. Exposing monocytes to heat shock (47°C, 20 min) induced a rapid and marked upregulation of hsp70 without evoking injury or apoptosis, suggesting that hsp70 conferred protection and survival. In accordance, when monocytes were rendered apoptotic by serum deprivation, a drastic downregulation of hsp70 occurred, which was accompanied by a reduced synthesis of the constitutive family member hsc70. However, induction of monocyte apoptosis by IL-4 increased hsp70 expression in a concentration and time-dependent fashion. A neutralizing antibody against IL-4 abolished hsp70 expression and apoptosis induction after IL-4 treatment and so excluded indirect effects. LPS rescued monocytes from apoptosis but did not alter hsp70 formation significantly. These findings suggest that, in monocytes, distinct apoptotic triggers induce different responses of hsp70 so that this molecule does not exert protection against cell death directly or in general.
Selective stimulation of G-CSF gene expression in macrophages by a stimulatory monoclonal antibody as detected by a luciferase reporter gene assay
Authors: Aoki Yoshiko , Sha Shiken , Mukai Hidehito , Nishi Yoshisuke 
Published: September 2022

Abstract
We have identified a stimulatory monoclonal antibody (mAb) from autoimmune mice that selectively stimulates granulocyte colony-stimulating factor (G-CSF) gene expression in a mouse macrophage cell line. The induction was observed not only in the cell line, but also in normal peritoneal macrophages. This mAb bound to the monocyte/macrophage cell lines and pre-B leukemia cell lines, but also in normal peritoneal macrophages, whereas it did not bind to normal T and B cells in the spleen or fibroblastic cell lines. It could even bind to a human promyelocytic leukemia cell line, when they were differentiated into monocytic cells. On Western blotting, this mAb mainly recognized an approximately 30-kDa band and it was unique because there have been no reports of membrane-associated proteins with a similar molecular mass found in macrophages. These results suggest that there could be a specific gateway molecule to induce G-CSF in macrophages.
DNA vaccination: antigen presentation and the induction of immunity
Authors: Shedlock Devon J , Weiner David B 
Published: September 2022

AbstractDNA vaccination, or genetic immunization, is a novel vaccine technology that has great potential for reducing infectious disease and cancer-induced morbidity and mortality worldwide. Since their inception, DNA vaccines have been used to stimulate protective immunity against many infectious pathogens, malignancies, and autoimmune disorders in animal models. Plasmid DNA encoding a polypeptide protein antigen is introduced into a host where it enters host cells and serves as an epigenetic template for the high-efficiency translation of its antigen. An immune response, which is mediated by the cellular and/or humoral arms of the immune system and is specific for the plasmid-encoded antigen, ensues. It is thought that “professional” antigen-presenting cells play a dominant role in the induction of immunity by presenting vaccine peptides on MHC class I molecules, following direct transfection or “cross”-presentation, and MHC class II molecules after antigen capture and processing within the endocytic pathway. The correlates of immunity can be manipulated according to many immunization parameters, including the method of vaccine delivery, presence of genetic adjuvants, and vaccine regimen. DNA vaccines first advanced to the clinic five years ago, and the initial picture of their utility in humans is emerging. However, further analysis is required to determine their ultimate efficacy and safety in human beings. This technology has acquired a strong foothold in the field of experimental immunotherapy, and it is hoped that it will eventually represent the next generation of prophylactic and therapeutic vaccines.
Activation of human neutrophils by the plant lectinViscum albumagglutinin-I: modulation ofde novoprotein synthesis and evidence that caspases are involved in induction of apoptosis
Authors: Savoie Anik , Lavastre Valérie , Pelletier Martin , Hajto Tibor , Hostanska Katarina , Girard Denis 
Published: September 2022

AbstractThe plant lectin Viscum album agglutinin-I (VAA-I) was recently found to modulate protein synthesis and to induce apoptosis in various cells of immune origin. We found that VAA-I induces de novo protein synthesis of metabolically 35S-labeled human neutrophils when used at low concentrations (&lt;100 ng/mL) but acts as an inhibitor at higher concentrations. Using both flow cytometry (FITC-Annexin-V/PI labeling) and cytology (Diff-Quick staining) approaches, we found that VAA-I could not modulate neutrophil apoptosis at low concentrations but could induce it in &gt;98% of cells at 500 and 1000 ng/mL. VAA-I was also found to reverse the delaying effect of GM-CSF on neutrophil apoptosis and to inhibit GM-CSF-inducedde novo protein synthesis. In contrast to GM-CSF, VAA-I does not induce tyrosine phosphorylation by itself and does not alter the GM-CSF-induced response. Among the inhibitors used, genistein, pertussis toxin, staurosporine, H7, Calphostin C, manoalide, BpB, quinacrine HA-1077, and z-VAD-FMK, only the latter (inhibitor of caspases-1, -3, -4, and -7) was found to inhibit VAA-I-induced neutrophil apoptosis as the percentage of apoptotic cells decrease from 98 ± 1.3 to 54 ± 3.2% (n =4). Furthermore, we confirm that caspases are involved in VAA-I-induced neutrophil apoptosis as we have observed the fragmentation of the cytoskeletal gelsolin protein that is known to be caspase-3-dependent. Such degradation was reversed by the z-VAD-FMK inhibitor. We conclude that induction of neutrophil apoptosis by VAA-I is a caspase-dependent mechanism that does not involve tyrosine phosphorylation events, G-proteins, PKCs, and PLA2. In addition, we conclude that at least caspase-3 is involved. Correlation between VAA-I-induced neutrophil apoptosis and VAA-I-induced inhibition of de novo protein synthesis is discussed.