bluuebunny/crossref_metadata_2025_split huggingface dataset:
Internalin A can mediate phagocytosis of Listeria monocytogenes by mouse macrophage cell lines
Authors: Sawyer Richard T , Drevets Douglas A , Campbell Priscilla A , Potter Terry A 
Published: January 2018

Abstract
Listeria monocytogenes internalin A (InlA) is a surface protein that mediates the attachment of Listeria to, and invasion of, hepatocytes, epithelial, and endothelial cells. In this study, we tested whether InlA could also mediate phagocytosis of L. monocytogenes by the non-listericidal mouse macrophage cell lines J774A.1 and H36.12j. Recombinant InlA (rInlA) was used to derive mouse monoclonal anti-InlA antibodies (mAb) and rabbit anti-InlA antibodies. Fluorescence microscopy demonstrated that these anti-InlA antibodies reacted with wild-type L. monocytogenes, L. ivanovii, and L. innocua+, a mutant transformed with the inlAB operon that expresses surface InlA but failed to react with Bug 8, an InlA/InlB-negative transposon mutant of L. monocytogenes or with non-invasive Listeria sp. Fluorescence microscopy, radiolabeling, and flow cytometry showed that rInlA bound specifically to both macrophage cell lines. Incubation of macrophages and wild-type L. monocytogenes in the presence of rInlA or pretreatment of Listeria with anti-InlA antibodies specifically inhibited, by at least 50%, the phagocytosis of Listeria by both of these cells. By comparison, treatment with these reagents failed to affect the phagocytosis of Streptococcus pyogenes by either macrophage cell line nor did these reagents alter the ability of macrophages to internalize wild-type L. monocytogenes. We found that Bug 8, but not wild-type L. monocytogenes, failed to grow within both of these non-listericidal macrophage cell lines. In contrast to infection by wild-type L. monocytogenes, Bug 8 was rapidly eliminated from the spleens of both C57B1/6 and DBA/2 mice. Data presented here show that only invasive Listeria sp. have surface InlA and that L. monocytogenes can enter non-listericidal macrophage cell lines by binding of bacterial InlA to the macrophage cell surface.
Peroxynitrite augments fMLP-stimulated chemiluminescence by neutrophils in human whole blood
Authors: Bednar Martin M , Balazy Michael , Murphy Michael , Booth Christina , Fuller Susan P , Barton Andrew , Bingham Jemel , Golding Lisa , Gross Cordell E 
Published: January 2018

Abstract
The neutrophil respiratory burst was examined by the technique of luminol-dependent chemiluminescence (LDCL) triggered by submaximal concentrations of N-formyl-methionyl-leucyl-phenylalanine (fMLP) in diluted whole blood. We sought to identify the chemical species responsible for LDCL in whole blood, to examine the role of leukotriene B4 (LTB4) and other arachidonic acid metabolites as mediators of the fMLP signaling pathway, and to investigate the effect of peroxynitrite on this response. Both sodium azide and taurine significantly inhibited LDCL (93% inhibition with 100 μM azide, 52% inhibition with 10 mM taurine). More modest inhibition was seen with superoxide dismutase (SOD), catalase, the nitric oxide synthase inhibitor monomethyl-l-arginine (l-NMMA), and with inhibitors of the cyclooxygenase (indomethacin), lipoxygenase (AA-861; no effect), and cytochrome P-450 (SKF 525-A) pathways of arachidonic acid metabolism. The nitric oxide donor SIN-1 (1–100 μM) and peroxynitrite (10–300 μM) also augmented fMLP-induced LDCL. The augmentation seen with peroxynitrite and SIN-1 was attenuated by SOD. Despite the increase in LDCL, peroxynitrite caused a dose-related inhibition of fMLP-stimulated LTB4 release. In summary, our results indicate that (1) LDCL elicited by fMLP in diluted whole blood appears primarily mediated by hypo-chlorous acid derived from myeloperoxidase; (2) pretreatment with the nitric oxide donor SIN-1 or with peroxynitrite augments LDCL; and (3) LTB4 release does not contribute to fMLP-stimulated LDCL or in the modulation of LDCL by SIN-1 or peroxynitrite.
Mechanisms involved in sodium arsenite-induced apoptosis of human neutrophils
Authors: William R , Watson G , Redmond H Paul , Wang Jiang Huai , Bouchier-Hayes David 
Published: January 2018

Abstract
Apoptosis is a distinct mechanism by which eukaryotic cells die. Factors governing the induction of polymorphonuclear leukocyte (PMN) apoptosis should be important in understanding resolution of acute inflammation. The mechanisms for induction of PMN apoptosis remain uncertain; however, oxidative stress has been suggested. The aims of this study were to determine whether reactive oxygen intermediates play a role in PMN apoptosis and to investigate inhibition of this process by selective use of antioxidants. PMN were isolated from 10 healthy volunteers. PMN (1 106 PMN/mL) were cultured in 40, 80, and 160 μM of arsenite for 2, 6, 12, 18, and 24 h. Apoptosis was assessed qualitatively by morphology and gel electrophoresis and quantitatively by CD16 receptor expression and propidium iodide DNA staining. There was a significant (P &lt; 0.05) increase in the rate of apoptosis on incubation with arsenite (80 and 160 μM). To investigate the mechanism of this process, intracellular respiratory burst activity was measured following arsenite culture. We found that arsenite-induced PMN apoptosis correlated with an increase in intracellular respiratory burst. To further investigate the role of oxidative injury in inducing apoptosis, the antioxidants catalase, dimethyl sulfoxide (DMSO), glutathione (GSH), N-acetylcysteine (NAC), and taurine were investigated and we demonstrated that GSH, NAC, and taurine were significantly protective against arsenite-induced apoptosis. However, catalase and DMSO failed to induce protection. This study demonstrates that arsenite induces PMN apoptosis through an oxygen-dependent mechanism that can be prevented through selective antioxidants.
Endotoxin-inducible granulocyte-mediated hepatocytotoxicity requires adhesion and serine protease release
Authors: Sauer Achim , Hartung Thomas , Aigner Joachim , Wendel Albrecht 
Published: January 2018

Abstract
In primary cultures of Kupffer cells and hepatocytes, human granulocytes potentiated toxicity of endotoxin about 1000-fold. Granulocyte elastase activity was found to correlate with toxicity. The serine protease inhibitors α1-antitrypsin, eglin C, and aprotinin protected against toxicity. Tumor necrosis factor-α (TNF-α) induced cytotoxicity and elastase release, whereas neutralization of TNF-α blocked both events. We conclude that TNF-α formed by Kupffer cells activates granulocytes. Experiments in cultures where cells were separated by membranes permeable to mediators indicated that cell contact is needed for toxicity. Scanning electron microscopy showed granulocytes adhering to and interdigitating with hepatocytes. Using liver cells from ICAM-1-deficient mice had no effect on toxicity. However, neutralizing CD31 inhibited toxicity and elastase release but not granulocyte adhesion. Our findings demonstrate that adhesion of granulocytes is a necessary but not sufficient condition for the synergistic interaction of endotoxin-stimulated liver macrophages and granulocytes in the proteolytic killing of hepatocytes.
Preparation of specific polyclonal antibodies to a C-C chemokine receptor, CCR1, and determination of CCR1 expression on various types of leukocytes
Authors: Su Shao-bo , Mukaida Naofumi , Wang Jian-bin , Nomura Hideki , Matsushima Kouji 
Published: January 2018

Abstract
cDNA cloning has revealed the presence of at least three distinct human receptors for macrophage inflammatory protein-1α (MIP-1α) and RANTES: C-C chemokine receptor (CCR) 1, 4, and 5. To clarify the physiological role of CCR1, we prepared specific antibodies to CCR1 by immunizing rabbits with recombinant glutathione-S-transferase (GST) fused with its NH2-terminal portion. The resultant antibodies stained positively 293 cells transfected with CCR1 cDNA but neither parental cells nor cells transfected with CXCR1 [interleukin-8 (IL-8) receptor type A] cDNA, confirming its specificity. Immunofluorescence analysis revealed that peripheral blood lymphocytes and monocytes but not neutrophils express CCR1. Positive staining of transfectants, monocytes, and lymphocytes was inhibited by the GST protein fused with the NH2-terminal portion of CCR1, further indicating that this antibody recognized the NH2-terminal portion of CC CKR1. A majority of CD3+, CD4+, CD8+, or CD16+ peripheral blood lymphocytes but not CD19+ lymphocytes expressed CCR1. Among CD4+ peripheral blood lymphocytes, CD45RO+ cells expressed a larger number of CCR1 compared with CD45RO-. Moreover, CD34+ cells in human bone marrow as well as cord blood were uniformly stained with this antibody. Furthermore, the antibody inhibited calcium mobilization in CCR1 transfectants stimulated with human rMIP-1α, suggesting that its NH2-terminal portion is critically involved in ligand binding or signaling. Finally, the antibody partially inhibited monocyte chemotactic activities of human rMIP-1α, suggesting that CCR1 is a functional receptor for MIP-1α on human peripheral blood monocytes.
Assembly of the phagocyte NADPH oxidase: molecular interaction of oxidase proteins
Authors: DeLeo Frank R , Quinn Mark T 
Published: January 2018

Abstract
Phagocytes such as neutrophils play a key role in the body's innate immune response to infection. These cells travel throughout the body in search of pathogens and are rapidly mobilized to sites of inflammation where they phagocytose these pathogens and subsequently release a variety of toxic oxygen radical species and proteolytic enzymes to directly destroy the engulfed particle. The generation of microbicidal oxidants by neutrophils results from the action of a multi-protein enzymatic complex known as the NADPH oxidase. Altogether, there are currently seven proteins reported to be associated with the NADPH oxidase assembly. In resting neutrophils, these NADPH oxidase protein components are segregated into cytoplasmic and plasma membrane compartments. However, during assembly and activation of the NADPH oxidase, the cytosolic protein components translocate to the plasma membrane or phagosomal membrane where they assemble around a central membrane-bound protein known as flavocytochrome b. This assembly process is highly regulated and involves multiple binding interactions between the individual NADPH oxidase proteins, resulting in an active oxidase complex. Over the past few years, a number of these sites of binding interaction between the oxidase proteins have been identified, leading to a clearer understanding of the intermolecular interactions occurring among protein components during the assembly process. In addition, this information has contributed to our understanding of the roles played by each protein during the activation and assembly process. In this review, we describe the key features of each NADPH oxidase protein and then summarize our current understanding of the specific molecular interactions occurring between these proteins, focusing on the role these protein:protein binding interactions play in the NADPH oxidase assembly process.
Effect of interferon-γ, in vitro and in vivo, on mRNA levels of phagocyte oxidase components
Authors: Weening Ron S , de Klein Angelique , de Boer Martin , Roos Dirk 
Published: January 2018

Abstract
Daring the international placebo-controlled trial on the efficacy of interferon-γ (IFN-γ) in chronic granulomatous disease (CGD), 19 patients entered the study via our Institute. One patient stopped treatment shortly thereafter. RNA was purified from the mononuclear cells of the remaining 18 CGD patients before and during this placebo-controlled trial. The mRNA levels for the NADPH oxidase components were subsequently analyzed. Compared with the placebo-treated CGD patients, the mRNA levels for p4 7-phox were significantly increased in the IFN-γ-treated CGD patients (P &lt; 0.002). No significant changes were observed in the mRNA levels of the other oxidase components. These findings are in agreement with observations in vitro and indicate that IFN-γ is active on the NADPH oxidase in vivo as well. However, it remains questionable whether these effects in vivo can explain the observed reduction of infections in these patients.
ICAM-1 expression and low-molecular-weight G-protein activation of human bronchial epithelial cells (A549) infected with RSV
Authors: Arnold R , König W 
Published: January 2018

Abstract
The airway epithefial cell of the lower respiratory tract is the primary host target cell for respiratory syncytial virus (RSV) infection. To estimate whether infected epithelial cells contribute to the inflammatory host response observed during the acute infection phase we analyzed the cell surface expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on human bronchial epithelial cells (A549) following RSV infection and cytokine priming. The epithelial cells constitutively expressed ICAM-1. The ICAM-1 surface expression was significantly up-regulated up to 72 h post RSV infection. In addition, cytokine priming with tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), or interleukin-1α/β (IL-1α/β) induced an enhanced ICAM-1 expression on noninfected as well as on RSV-infected epithelial cells. As early as 24 h post RSV infection and cytokine priming, respectively, the maximum of ICAM-l-expressing cells was observed. In contrast, the maximal ICAM-1 up-regulation per cell was measured 24 h later, e.g., after 48 h of culture. Cytokine priming with IL-3, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte colony-stimulating factor (G-CSF) did not lead to a significant increase of ICAM-1 expression either on RSV-infected or on noninfected A549 cells up to 72 h of culture time. Performed signal transduction experiments, e.g. [α-32P]GTP-binding blot analysis, revealed that low-molecular-weight GTP-binding proteins possess an enhanced GTP-binding capacity in RSV-infected A549 cells.
Monocytic differentiation modulates apoptotic response to cytotoxic anti-Fas antibody and tumor necrosis factor α in human monoblast U937 cells
Authors: Kikuchi Hidehiko , Iizuka Ryoko , Sugiyama Shinji , Gon Gotetsu , Mori Hiroyuki , Arai Masa-aki , Mizumoto Kiyohisa , Imajoh-Ohmi Shinobu 
Published: January 2018

Abstract
Interferon-γ (IFN-γ), vitamin D3 (VD), and retinoic acid (RA) induce differentiation of human monoblastic leukemia U937 cells to macrophage-like cells with potential superoxide anion-generating activity upon further stimulation. Here we report that U93 7 cells thus differentiated show various responses to apoptotic induction with a cytotoxic anti-Fas antibody and tumor necrosis factor (TNF). VD-or RA-treated U937 cells acquired resistance against Fas- or TNF receptor (TNFR)-mediated apoptosis, whereas apoptotic cell death was accelerated in IFN-γ-treated cells. By flow cytometric analyses, no decrease in expression of surface Fas antigen or p55 TNFR was observed in differentiated U937 cells. Cell surface expression of CD11b was seen only when differentiation was induced with VD or RA but not with IFN-γ. The growth of VD- or RA-treated cells was retarded but IFN-γ-treated cells were prolific. These findings suggest that the differentiation state differs with the inducer and that the cellular response to apoptotic induction is closely related to the state including the cell cycle.
LPS pretreatment reprograms macrophage LPS-stimulated TNF and IL-1 release without protein tyrosine kinase activation
Authors: West Michael A , Bennett Terriel , Seatter Susan C , Clair Laurel , Bellingham Janet 
Published: January 2018

Abstract
Pretreatment of macrophages with low-dose endotoxin (LPSp) profoundly alters cytokine release in response to subsequent LPSa activation. These qualitative and quantitative alterations in cytokine release have been termed macrophage reprogramming. Macrophage activation by LPS is thought to occur via a mechanism involving an early protein tyrosine kinase (PTK) phosphorylation step. PTK inhibition with genistein or herbimycin A blocks LPSa-stimulated secretion of tumor necrosis factor (TNF) and interleukin-1 (IL-1). In this study we investigated whether a PTK pathway participates in LPSp pretreatment reprogramming. We show that LPSp pretreatment inhibited TNF and augmented IL-1 release in response to subsequent LPSa stimulation. Blockade of PTK activation pathways during the interval when macrophages were exposed to LPSp prevented mitogen-activated protein kinase phosphorylation, as well as LPSp-stimulated release of TNF and IL-1, but did not block LPSp reprogramming effects. We conclude that LPSp pretreatment reprogramming of macrophage cytokine production does not require PTK activation.
IgM-mediated opsonization and cytotoxicity in the shark
Authors: McKinney E C , Flajnik Martin F 
Published: January 2018

Abstract
Two types of cytotoxic reactions have been observed using cells from the nurse shark: spontaneous cytotoxicity mediated by cells of the macrophage lineage and antibody-dependent killing carried out by a different effector cell population. Previous data showed that removal of phagocytic cells using iron particles abolished macrophage-mediated killing, but not antibody-dependent reactions. The current study used single cell assays and showed that the effector of antibody-driven reactions was the neutrophil. Surprisingly, the mechanism of killing was shown to be phagocytosis mediated by both 7S and 19S immunoglobulin M (IgM). Reactions proceeded with as little as 0.01 μg of purified 19S or 7S IgM and were complete within 4–6 h. In contrast, purified immunoglobulin did not adsorb to macrophages and had no effect on target cell binding or cytotoxicity. Pretreatment of cells with cytochalasin D abolished the phagocytic reaction, but not spontaneous cytotoxicity. These data show that antibody-mediated killing results from opsonization and phagocytosis; the mechanism of macrophage killing is currently unknown. In addition, these data show that the shark neutrophil, not the macrophage lineage, carries a receptor for Fcμ.
Fas involvement in human NK cell apoptosis: lack of a requirement for CD16-mediated events
Authors: Ortaldo John R , Winkler-Pickett Robin T , Nagata Shigekazu , Ware Carl F 
Published: January 2018

Abstract
Propriocidal regulation of T cells refers to apoptosis induced by interleukin-2 (IL-2) activation with subsequent antigen receptor stimulation. We previously reported that natural killer (NK) cells also exhibit propriocidal death. Cell death can be induced following occupancy of the FcγRm (CD16) receptor when NK cells were pretreated with IL-2, IL-12, or IL-15. Here we show other triggering receptors on NK cells such as CD44, anti-NK-receptor antibodies, and pharmacological activation can result in the cell death signal. Requirement for cell interactions indicated that cell contact was required; however, unlike cell-mediated lysis, extracellular calcium was not required. Like T cells, the process of cell death for NK cells was receptor-induced apoptosis. Activation-induced apoptosis of T cells is mediated by members of the tumor necrosis factor (TNF) cytokine superfamily. We examined the involvement of TNF receptor family members or Fas in this rapid cell death. Antibody directed against Fas, TNFR60, TNFR80, LTBR, and LTα failed to inhibit receptor-induced death. Therefore, NK cells appear to demonstrate a rapid apoptotic episode when CD16 is cross-linked, but the mechanism of this apoptosis is quite different than was observed in T cells with CD3. The direct examination of the Fas pathway on activated NK cells revealed that susceptibility required longer treatment times and IL-2 activation. This susceptibility was paralleled by increased Fas-ligand expression. Therefore, NK cells can demonstrate an apoptotic response to CD16, CD44, NK receptors, and Fas. The enumeration of ligands capable of eliciting NK cell death and the in vivo relevance of this observation require further study.
Studies with IL-10-/- mice: an overview
Authors: Rennick Donna M , Fort Madeline M , Davidson Natalie J 
Published: January 2018

Abstract
Our studies have elucidated, in part, the mechanism whereby persistent stimulation by normal enteric antigens leads to the development of chronic enterocolitis in interleukin 10-deficient (IL-10-/-) mice. This disease is mediated by IL-10-/-CD4+ T cells as evidenced by their ability to transfer colitis to immunodeficient RAG-2-/-mice. Furthermore, the CD4+ T cells recovered from the affected colons of IL-10-/- mice consisted of a highly polarized Th1-like population because they produced interferon-γ (IFN-γ) but not IL-4. We found that enterocolitis could be prevented if 3-week-old mutants were treated for 6–8 weeks with either anti-IL-12 or anti-IFN-γ monoclonal antibodies (mAb). These results were consistent with the findings of in vitro studies suggesting that IFN-γ and, in particular, IL-12 direct the differentiation of naive T cells toward a Th1 phenotype. Apparently, the uncontrolled production of IL-12 and IFN-γ by accessory cells and T cells, respectively, in IL-10-/- mice ultimately resulted in the excessive generation and activation of Th1 cells, hence, immunopathology. IL-10-/- mice have also been used to evaluate the importance of IL-10 in regulating immune responses outside of the gastrointestinal (GI) tract. In these studies, IL-10-/-mice were challenged with a variety of foreign antigens using different routes of administration. In general, the results repeatedly demonstrated that a major function of IL-10 is to protect the host from the harmful side effects of an overly zealous immuneinflammatory response. However, other studies have confirmed speculations that the potent immunosuppressive activities of IL-10 may, under certain circumstances, increase the host's susceptibility to infection with certain types of pathogenic organisms.
Susceptibility of mononuclear phagocytes to influenza A virus infection and possible role in the antiviral response
Authors: Hofmann P , Sprenger H , Kaufmann A , Bender A , Hasse C , Nain M , Gemsa D 
Published: January 2018

Abstract
Among leukocytes, only monocytes and macrophages were found to be highly susceptible to an infection by influenza A virus. After infection, de novo viral protein synthesis was initiated but then interrupted after 4–6 h. Most macrophages died by apoptosis within 25–30 h. Before cell death, however, macrophages responded to influenza A virus with a high cytokine gene transcription and subsequent release of tumor necrosis factor α (TNF-α), interleukin-1 (IL-1), IL-6, interferon (IFN) -α/β, and CC-chemokines. The basic mechanisms of virus-induced cytokine expression are still unknown and appear to involve transcription factors such as nuclear factor-κB and AP-1 which, however, were only activated for 2 h and declined below control values thereafter. After influenza A virus infection, only the mononuclear cell attracting CC-chemokines macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and RANTES were produced while the prototype neutrophil CXC-chemoattractants IL-8 and GRO-α were entirely suppressed. This selective induction of CC-chemokines may explain the preferential influx of mononuclear leukocytes into virus-infected tissue. Our data show that monocytes and macrophages represent a primary target for an influenza A virus infection. Thus, the mononuclear phagocyte response leads to a rapid proinflammatory reaction and an enhanced immigration of mononuclear leukocytes, which may condition the infected host for the subsequent virus antigen-specific defense.