bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of YopH in the suppression of tyrosine phosphorylation and respiratory burst activity in murine macrophages infected with Yersinia enterocolitica
Authors: Green Simon P , Hartland Elizabeth L , Robins-Browne Roy M , Phillips Wayne A 
Published: January 2018

Abstract
Tyrosine phosphorylation is an important component of the signaling pathways responsible for the activation of the macrophage respiratory burst. Because the virulence plasmid of Yersinia enterocolitica encodes a phosphotyrosine phosphatase, YopH, it is possible that the pathogenic strategy of Y. enterocolitica involves the disruption of tyrosine phosphorylation in the macrophage leading to inhibition of respiratory burst activity. We have investigated the effects of Yersinia infection on tyrosine phosphorylation and respiratory burst activity in murine bone marrow-derived macrophages. Infection of macrophages with virulent [Ye(pYV+)] but not avirulent [Ye(pYV-)] strains of Y. enterocolitica was found to suppress both tyrosine phosphorylation and respiratory burst activity in response to zymosan. Mutational inactivation of YopH reversed the suppressive effect of Ye(pYV+) on zymosan-induced tyrosine phosphorylation, indicating that YopH is responsible for the dephosphorylation of macrophage phosphotyrosine-containing proteins observed in macrophages infected with the virulent strain of Y. enterocolitica. In contrast, mutational loss of YopH failed to reverse the inhibitory effect of Ye(pYV+) on the zymosan-triggered respiratory burst. We conclude that the inhibition of the macrophage respiratory burst by Y. enterocolitica involves a plasmid-encoded virulence protein(s) other than, or in addition to, YopH J. Leukoc. Biol. 57: 972–977; 1995.
Dissociation of Rac translocation from p47phox/p67phox movements in human neutrophils by tyrosine kinase inhibitors
Authors: Dorseuil Olivier , Quinn Mark T , Bokoch Gary M 
Published: January 2018

Abstract
Cytosolic components of the phagocyte NADPH oxidase (p47phox, p67phox, and Rac2) translocate to the plasma membrane on cell activation where they interact with a membrane-bound cytochrome b to generate superoxide anion. Phosphorylation reactions are known to be important for activity of NADPH oxidase. Translocation of Rac2, p47phox, and p67phox were all enhanced in formyl-Met-Leu-Phe-stimulated neutrophils treated with 50 nM of the protein phosphatase 1/2A inhibitor calyculin A. Rac translocation was blocked by the tyrosine kinase inhibitors genistein (50 μM) and herbimycin (17 μM), whereas movement of p47phox and p67phox were not inhibited. Cell-free analysis of Rac translocation also demonstrated that translocation of p47phox and p67phox were not linked to the movement or availability of Rac2. Thus, Rac2 does not appear to regulate NADPH oxidase by controlling movements of the cytosolic components to the membrane-associated enzyme but may exert its effect at the level of the assembled complex. Tyrosine kinase activity is required for translocation of Rac in the chemoattractant-stimulated human neutrophil. J. Leukoc. Biol. 58: 108–113; 1995.
Hyperglycosylation of eosinophil ribonucleases in a promyelocytic leukemia cell line and in differentiated peripheral blood progenitor cells
Authors: Lee Tiffany H , Li Fei , Rosenberg Helene F 
Published: January 2018

Abstract
We evaluated two independent models of eosinophil differentiation for their ability to synthesize the ribonuclease toxins eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP). Cells from the done 15 subline of HL-60 (human promyelocytic leukemia) produced both EDN and ECP; production of EDN increased in response to butyric acid (BA). CD34+ peripheral blood progenitor cells (PBPCs) grown with cytokines promoting eosinophil differentiation also produced EDN. EDN from both the done 15 and PBPCs was more heterogeneous and heavily glycosylated (~22–45 kDa) than EDN from mature peripheral blood eosinophils (18–25 kDa). The heterogeneity of EDN from the done 15 cells was not altered by endogiycosidase Hf, whereas treatment with peptide-N-giycosidase F (PNGase F) produced a single-band immunoreactive band (~15 kDa). In contrast, only the highest molecular weight forms of EDN from differentiated PBPCs were eliminated by PNGase F (reduced to 22–35 kDa), suggesting the presence of uncharacteristic forms of posttranslational modification. Synthesis of hyperglycosylated proteins has not been previously reported in PBPCs and is a feature shared with tumor cells and cell lines. J. Leukoc. Biol. 58: 49–54; 1995.
Modulation of human microglial cell superoxide production by cytokines
Authors: Chao Chun C , Hu Shuxian , Peterson Phillip K 
Published: January 2018

Abstract
Reactive oxygen intermediates (e.g., superoxide [O2-]) generated by microglia may play a role in host defense and injury within the central nervous system. We investigated the effect of cytokines on human microglial cell O2- production on stimulation with phorbol myristate acetate. Priming of microglial cell cultures with interferon-γ or tumor necrosis factor-α resulted in a dose- and time-dependent enhancement of (O2- production. The priming effects of these cytokines were mediated through a protein kinase C signal transduction pathway. In contrast, astrocytes did not generate detectable O2- on phorbol myristate acetate stimulation. Treatment of microglia with transforming growth factor-β, interleukin-4, or interleukin-10 suppressed in a dose-dependent manner the priming effects of tumor necrosis factor-α and interferon-γ. The results of this study have implications for understanding the mechanisms by which cytokines and microglia contribute to processes of host defense and neurodegeneiration via generation of reactive oxygen intermediates. J. Leukoc. Biol. 58: 65–70; 1995.
IL-1 activation of endothelium supports VLA-4 (CD49d/CD29)-mediated monocyte transendothelial migration to C5a, MIP-1α, RANTES, and PAF but inhibits migration to MCP-1: a regulatory role for endothelium-derived MCP-1
Authors: Chuluyan H Eduardo , Schall Thomas J , Yoshimura Teizo , Issekutz Andrew C 
Published: January 2018

Abstract
We investigated the effect of interleukin-1 (IL-1) activation of human umbilical vein endothelium (HUVE) on human monocyte transendothelial migration induced by chemotactic factors. Monocyte migration across unacdvated endothelium in response to macrophage inflammatory protein-lα (MIP-1α), RANTES, platelet-activating factor (PAF), or monocyte chemoat-tractant protein-1 (MCP-1) was completely inhibited (90%) by monoclonal antibodies (mAbs; 60.3) to CD 18 of the CD11/CD18 complex on the monocyte and partially inhibited (by 75%) in response to C5a. When the HUVE was stimulated with IL-lα (5 h, 0.1 ng/ml), monocyte migration in response to C5a, MIP-lα, RANTES, or PAF was no longer inhibited by mAb to CD18. However, migration was blocked by the combination of mAb to the (α4-integrin (CD49d) chain of very late antigen-4 (CD49d(/CD29) with the mAb to CD18. In contrast to the above stimuli, activation of the HUVE with IL-1α inhibited the transendothelial migration of monocytes in response to MCP-1. mAbs to the adhesion molecules up-regulated on HUVE by IL-1, i.e., E-selectin (CD62E), intercellular adhesion molecule-1 (CD54) or vascular cell adhesion molecule-1 (CD106), did not reverse the inhibitory effect. Transendothelial migration in response to MCP-1 but not to C5a was inhibited by the treatment of monocytes with culture supernatant from IL-1α-stimulated (but not from unstimulated) HUVE. Such supernatant contained chemotactic activity for monocytes, and a mAb to MCP-1 blocked the migration inhibitory effect of IL-1 activation of the HUVE monolayer, as well as the chemotactic activity in the supernatant from IL-1-stimulated HUVE. The inhibitory effect on migration of IL-1-stimulated HUVE was specific for monocytes because polymorphonuclear leukocyte transendothelial migration in response to IL-8 (a related chemokine) was not inhibited by IL-1 activation of HUVE. These results demonstrate that: (1) C5a but not MCP-1, MIP-lα, RANTES, or PAF activates not only a CD 18-dependent but also a VLA-4-dependent mechanism on monocytes, which mediates migration across unstimulated HUVE; (2) IL-1 (tumor necrosis factor-α or lipopolysaccharide) activation of HUVE results in efficient VLA-4 (CD494/CD29)-mediated monocyte transendothelial migration in response to C5a, RANTES, MIP-1α, and PAF, in addition to the CD 18-dependent pathway, but inhibits the response to MCP-1; and (3) this selective inhibition is probably due to MCP-1 production by the activated endothelium monolayer and may be one mechanism of down-regulation by the endothelium of monocyte migration in response to extravascular MCP-1. J. Leukoc. Biol. 58: 71–79,1995.
Nitric oxide stimulates ADP ribosylation of actin in association with the inhibition of actin polymerization in human neutrophils
Authors: Clancy Robert , Leszczynska Joanna , Amin Ashok , Levartovsky David , Abramson Steven B 
Published: January 2018

Abstract
In these studies we provide conclusive evidence that (β/γ) actin present in human neutrophils is a substrate for nitric oxide (NO)-dependent ADP ribosylation and that this modification is associated with the inhibition of actin polymerization. A 43-kDa substrate for NO-dependent ADP ribosylation was identified as actin by four methods: (1) comigration with the botulinum C2 toxin substrate by two-dimensional gel electrophoresis (pI 5.2), (2) identity between the peptide map generated by V8 protease digestion of the NO and botulinum C2 substrates, (3) immunoprecipitation with antiactin antibodies, and (4) the ability of NO to ADP ribosylate purified neutrophil G-actin in the presence of plasma membrane cofactors. Because the ADP ribosylation of actin by the botulinum C2 toxin is known to inhibit F-actin polymerization, we examined the effect of NO on actin assembly. Flow cytometry revealed that NO inhibited formyl-methionine-leucine-phenylalanine (fMLP)-dependent (SO s at 37°) F-actin formation (108 ± 8 vs. 89 ± 6 relative fluorescence units, P &lt; .02). These results were confirmed by quantification of F-actin formation by gel scanning (10% sodium dodecyl sulfate gel, Coomassie, and densitometry): pretreatment of polymorphonuclear leukocytes with NO resulted in a reduction of fMLP-induced, cytoskeletal-associated F-actin, which was accompanied by an increase of Triton-soluble G-actin. NO also inhibited F-actin formation, as observed by means of rhodamine phalloidin staining of neutrophils adherent to a fibronectin-coated surface. This effect was accompanied by a dose-dependent inhibition of neutrophil adherence in NO-treated cells. The data indicate that NO inhibits cytoskeletal assembly and adherence in human neutrophils in association with the ADP ribosylation of actin. J. Leukoc. Biol. 58: 196–202; 1995.
Low-molecular-weight GTP-binding proteins and leukocyte signal transduction
Authors: Quinn Mark T 
Published: January 2018

Abstract
Recent progress on the understanding of leukocyte signal transduction pathways indicates that many of these pathways are modulated by low-molecular-weight GTP-binding proteins (LMWGs). LMWGs are members of a growing family of GTP-binding proteins known as the Ras superfamily and act as molecular switches for regulating a wide range of signal-transduction pathways in virtually all cells. In leukocytes, LMWGs have been shown to participate in essential cellular functions such as growth control, differentiation, cytoskeletal organization, cytokine and chemoattractant-induced signaling events, reduced nicotinamide adenine dinucleotide phosphate oxidase activity, phospholipid metabolism, and intracellular vesicle transport and secretion, and many more of these functions will certainly be identified as we gain a further understanding of regulatory pathways modulating leukocyte signal transduction. This review will summarize our current understanding of this rapidly advancing area of research.
Taurolidine, an antilipopolysaccharide agent, has immunoregulatory properties that are mediated by the amino acid taurine
Authors: William R , Watson G , Redmond H Paul , Carthy Julie Mc , Bouchier-Hayes David 
Published: January 2018

Abstract
Taurolidine has bactericidal and antilipopolysaccharide properties. It is broken down into the amino acid taurine, which has been shown to modulate intracellular calcium activity, a critical component in the priming and activation of macrophages and polymorphonuclear leukocytes. We hypothesized that taurolidine may function to enhance immune activity in these cells. The aim of this study was to investigate the immunological effects of taurolidine and correlate findings with survival after a septic challenge in a murine model. Study 1: CD-1 mice underwent cecal ligation and puncture, were randomized to receive taurolidine (200 mg/kg body weight/i.p.) or saline control, and studied for end point survival. Study 2: CD-1 mice were randomized to receive taurolidine (200 mg/kg body weight/i.p.) or saline control. Peritoneal macrophages (PMØs) were assessed for O2-, NO, tumor necrosis factor-α (TNF-α), CD11b, phagocytosis, and PMN influx. O2-, TNF-α, CD11b expression, and phagocytosis were significantly increased in the taurolidine group. Study 3: PMØs were cultured in vitro ±0.5 mg/ml taurolidine and PMØ antimicrobial function assessed (O2-, NO, TNF-α, and phagocytosis). O2-, TNF-α, and phagocytosis were significantly increased, whereas NO was reduced. Study 4: PMØs were also cultured with taurine (0.5 mg/ml). Similar increase in O2-, TNF-α, and phagocytosis were identified. Intracellular PMØ [Ca2+] was also assessed and increases in free, unbound intracellular [Ca2+] occurred after taurine culture. Thus, in addition to its bactericidal and antilipopolysaccharide activity, taurolidine primes PMØs for enhanced antimicrobial activity and these effects appear mediated by the amino acid taurine.
Pleural fluid eosinophils suppress local IgE-mediated protein exudation in rats
Authors: Bandeira-Melo Christianne , Silva Patricia M R e , Cordeiro Renato S B , Martins Marco A 
Published: January 2018

Abstract
Eosinophils are supposed to play a critical role in the pathology of several allergic diseases because after activation they can release toxic and proinflammatory agents. In this study we have investigated whether IgE-mediated rat pleurisy could be affected by an ongoing pleural eosinophilic inflammatory response. IgE-passively sensitized rats were challenged with an intrapleural (i.pl.) injection of allergen (dinitrophenylated bovine serum albumin, 1 μg/cavity) and exudation assessed by measuring the amount of protein extravasated into the pleural cavity within 4 h. We have confirmed that lipopolysaccharide (LPS) stimulation (250 ng/cavity i.pl.) was followed by a marked pleural neutrophilia, apparent at 3 h, which was followed by an eosinophil accumulation noted within 48–72 h postchallenge. We have also confirmed that a boiled sample of LPS pleural washing (IPS-PW, 200 μl i.pl.) caused selective eosinophilia in recipient rats. Pleural exudation remained unaltered when the allergenic challenge was performed 3 h after IPS in a condition of intense pleural fluid neutrophilia. In contrast, this was significantly reduced (P&lt; .001) when the challenge occurred 72 h after IPS or 24 h after IPS-PW in selective pleural fluid eosinophilia. In another series of experiments repeated daily i.pl. injections of platelet-activating factor (PAF; 1 μg/cavity) resulted in a progressive increase in eosinophil number recovered from the pleural cavity. The values were 1.2 ± 0.2, 3.0 ± 0.2, and 5.8 ± 0.5 × 106 eosinophils/cavity (mean±SEM) after 0, 1, and 4 injections, respectively. Allergen challenge performed after 0, 1, or 4 PAF stimulations led to pleural protein levels of 88.6 ± 5.7, 33.7 ± 0.7, and 19.4 ± 2.3 mg/cavity, respectively, indicating that the allergic pleurisy is inhibited in a manner dependent on the magnitude of eosinophil accumulation. Furthermore, the impairment of PAF-induced eosinophil accumulation by cetirizine (30 mg/kg i.p.) restored the exudatory response. Exudation triggered by compound 48/80 (25 μg/cavity), histamine (200 μg/cavity), or 5-hydroxytryptamine (100 μg/cavity) was not affected by four previous PAF daily injections. The findings indicate that allergen-induced exudation is selectively down-regulated in the eosinophil-enriched pleural space of rats, a suppression that increased with increasing eosinophil number and disappeared after chemical impairment of the eosinophilia.
Neutrophil functional responses depend on immune complex valency
Authors: Strohmeier Gregg R , Brunkhorst Beatrice A , Seetoo Kurt F , Bernardo John , Weil Gary J , Simons Elizabeth R 
Published: January 2018

Abstract
Ligand-induced cross-linking of Fcγ receptors (FcγR) on neutrophils plays a significant role in their stimulation, shown here by contrasting the responses induced by low valency immune complexes (LICs) and high valency immune complexes (HICs) and by cross-linking LICs in situ (L/Ab) after their addition to the cells. Multiparameter flow cytometry was used to measure immune complex (IC)-elicited changes in cytoplasmic Ca2+ concentration and initiation of the oxidative burst simultaneously in the same cell and to correlate these with FcγR occupancy. We have previously shown that subpopulations of neutrophils respond maximally to subsaturating concentrations of HIC; saturating dosages stimulate the entire population. This discrepancy was not due to differences in receptor occupancy. The magnitude of the transient Ca2+ increase was independent of the dose of HIC but depended on the dose when an LIC was used. As shown here, L/Ab cross-linking elicited Ca2+ responses similar to those observed in HIC-stimulated cells. In contrast, LIC elicited only minimal intracellular ΔpH and no oxidative burst or membrane potential changes at all unless FcγR was cross-linked, accomplished by HIC or by L/Ab. However, azurophilic degranulation, as determined by elastase release, was not observed in cells stimulated by the in situ cross-linking method, whereas the HIC preparation triggered azurophilic degranulation. Thus, some FcγR-mediated neutrophil effector functions such as azurophilic degranulation and oxidative burst initiation have an absolute requirement for FcγR cross-linking, whereas signaling functions such as changes in membrane potential, intracellular pH, and intracellular Ca2+ concentration can occur, albeit more slowly and to a lesser extent, if single FcγR are occupied.
Evidence for a third component in neutrophil aggregation: potential roles of O-linked glycoproteins as L-selectin counter-structures
Authors: Bennett Teresa A , Schammel Christine M G , Lynam Eric B , Guyer Deborah A , Mellors Alan , Edwards Bruce , Rogelj Snezna , Sklar Larry A 
Published: January 2018

Abstract
The homotypic aggregation of neutrophils requires the participation of L-selectin and the β2-integrins, but it has not been clear whether the two receptors recognize one another as counter-structures or whether other adhesion molecules are involved. We have examined aggregation of live neutrophils with target populations, manipulated to alter expression of adhesive epitopes, using flow cytometry. A target population depleted of both L-selectin and activatable β2-integrin displayed an ability to aggregate with live neutrophils, suggesting that these two molecules are not counter-structures. We also found that an O-sialoglycoprotease (GCP) from Pasteurella haemolytica is capable of inhibiting homotypic aggregation. Neutrophils treated with GCP lose O-glycosylated proteins but retain L-selectin and activatable β2-integrin. One or more of the GCP substrates appears to function in L-selectin-dependent binding but not in β2-integrin-dependent binding. Together the data suggest a mechanism of aggregation that is analogous to leukocyte-endothelial cell adhesion in which a low-affinity carbohydrate-dependent interaction precedes a high-affinity integrin-dependent adhesion.
Differential regulation of TNF-α production by listeriolysin-producing versus nonproducing strains of Listeria monocytogenes
Authors: Vazquez M A , Sicher S C , Wright W J , Proctor M L , Schmalzried S R , Stallworth K R , Crowley J C , Lu C Y 
Published: January 2018

Abstract
Only Listeria monocytogenes that produce listeriolysin O (LLO) elicit protective immunity. Given the importance of tumor necrosis factor α (TNF-α) in anti-Listeria immunity, we have investigated TNF-α production by macrophages after they ingested live LLO-producing compared to LLO-non-producing bacteria. We used two genetically engineered strains of Listeria that differed only in their ability (Ly+) or inability (Ly-) to produce LLO. Ly+ and Ly- caused the same kinetics of increased mRNA abundance for TNF-α during the first 90 min after phagocytosis. However, only Ly+ caused sustained transcription of TNF-α mRNA, and this may account for the increased release of TNF-α. The transcriptional inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) prevented the sustained abundance of cytokine mRNA 20 h after ingestion of Ly+. In addition, nuclear run-on assays indicated sustained transcription of TNF-α genes only after ingestion of Ly+. LLO itself was not responsible for the ability of Ly+ to stimulate the sustained transcription of the TNF-α genes. Instead, LLO may allow Listeria to survive within macrophages so that other bacterial products cause sustained TNF-α gene transcription. Both Ly+ and Ly- produced molecules, isolated by 50% ammonium sulfate, that induced cytokine production. In conclusion, we now report that Ly+ causes sustained transcription of the TNF-α gene and production of TNF-α by macrophages in vitro. We speculate that the TNF-α may activate endothelium and thus allow the recruitment of T cells to sites of infection. This may contribute to the ability of only LLO-producing Listeria to induce protective immunity.
Vitamin E supplementation with interferon-γ administration retards immune dysfunction during murine retrovirus infection
Authors: Wang James Y , Liang Bailin , Watson Ronald R 
Published: January 2018

Abstract
Murine retrovirus infection induces loss of vitamin E and immune dysfunction with loss of cytokine production by T-helper cells. Therefore interferon-γ (IFN-γ) was given during dietary vitamin E supplementation to effectively prevent murine retrovirus-induced immunosuppression, cytokine dysregulation, and development of murine AIDS. Administration of IFN-γ during vitamin E supplementation significantly prevented development of retrovirus-induced suppression of splenic natural killer cell activity and T cell proliferation. It also significantly slowed retrovirus-induced elevation of T helper (Th) 2 cytokine [interleukin (IL)-4, IL-5, and IL-10] production and monokine (IL-6 and tumor necrosis factor-α) secretion by splenocytes. The treatment also prevented loss of Th1 cytokine (IL-2 and IFN-γ) secretion by splenocytes from retrovirus-infected mice alleviating splenomegaly and hyper-gammaglobulinemia. The combined therapy had an additive therapeutic impact. It was more effective than IFN-γ treatment or vitamin E supplementation alone in delaying the development of retrovirus-induced immunosuppression with its cytokine dysregulation.