bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eosinophils inhibit retroviral transduction of human target cells by a ribonuclease-dependent mechanism
Authors: Domachowske Joseph B , Rosenberg Helene F 
Published: January 2018

Abstract
Human eosinophils contain a number of granule proteins for which specific physiological roles remain unclear. The combined ribonucleolytic and membrane disruptive properties of the eosinophil-derived neurotoxin and eosinophil cationic protein, respectively, suggest the possibility that eosinophils might participate in host defense against enveloped single-stranded RNA viruses. To test this hypothesis, stocks of a replication-defective retrovirus encoding the reporter gene β-galactosidase were pretreated with isolated human eosinophils, then used to transduce human erythroleukemia (K-562) target cells. Histochemical staining for β-galactosidase activity was used to detect and quantitate the transduced cells. Co-incubation of retrovirus with eosinophils (0.4 X 106/mL) before target cell transduction resulted in a marked decrease in transduction efficiency corresponding to an ~ 20-fold dilution of viral stock (P &lt; 0.01), an effect that was directly proportional to the concentration of eosinophils, and that was reversed in the presence of ribonuclease inhibitor. Reverse transcriptase-polymerase chain reaction analysis demonstrated loss of the retroviral RNA genome as a result of eosinophil pretreatment, indicating that eosinophils are capable of mediating direct ribonucleolytic destruction of the isolated retroviral particles. Our results demonstrate that eosinophils function as effective anti-retroviral agents in vitro via the actions of their secreted ribonucleases, and suggest that eosinophils may represent an unrecognized arm of host defense against enveloped single-stranded RNA viral pathogens.
The Ly-49 family: regulation of cytokine production in murine NK cells
Authors: Ortaldo J R , Mason L H , Gregorio T A , Stoll J , Winkler-Pickett R T 
Published: January 2018

Abstract
Most proteins encoded by members of the Ly-49 gene family are class I-recognizing receptors on murine natural killer (NK) cells. Class I recognition by Ly-49 receptors usually results in inhibition of NK cell lysis of target cells. However, NK cells function not only in a lytic capacity, but also can mediate cytokine production. In this report we have demonstrated the ability of Ly-49A and Ly-49G2 to inhibit production of cytokines by NK cells by showing that specific antibodies against these gene products stimulate cytokine production. Murine NK cells were cultured in the presence of P815 (H2-Dd), and supernatants were analyzed for the production of interferon-γ (IFN-γ), tumor necrosis factor α (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF). NK cell populations were sorted for Ly-49A+ or Ly-49G+ subsets, and these subsets were analyzed for their ability to alter cytokine induction by target cell interaction. In the presence of target cells expressing the appropriate class I molecules, Ly-49A and G2 were found to inhibit cytokine induction by NK cells. Examination of mRNA for IFN-γ and GM-CSF indicated that Ly-49 receptors increased mRNA levels of NK cells. These results demonstrate that class I binding of these NK receptors can inhibit production of important physiological cytokines, in addition to the regulation of cytotoxic activity.
Effects of dexamethasone treatment on IL-1 receptor mRNA levels in vivo
Authors: Yu Pei-Wen , Schuler L A , Kehrli M , Mattocks L , Nonnecke B J , Czuprynski C J 
Published: January 2018

Abstract
Using semiquantitative reverse transcriptase-polymerase chain reaction and Northern analysis, we observed in vivo up-regulation of interleukin-1 (IL-1) RI and IL-1RII mRNA levels in peripheral blood mononuclear cells (PBMCs) and neutrophils (PMNs) from Holstein cattle injected with dexamethasone (0.04 mg/kg). Baseline levels of IL-1RI mRNA were greater than IL-1RII mRNA levels in PBMCs and PMNs before dexamethasone treatment. This is in contrast with the previously reported predominance of IL-1RII in unstimulated human PMNs. IL-1RII mRNA was strongly induced in both bovine PBMCs and PMNs at 24 h and returned to baseline levels by 72 h, after dexamethasone injection. Conversely, the greatest increase in IL-1RI mRNA in PBMCs and PMNs was not detected until 72 h after dexamethasone injection. These data provide evidence for sequential in vivo up-regulation of first IL-IRII mRNA and later IL-1RI mRNA by dexamethasone that is consistent with the anti-inflammatory activity of glucocorticoids.
Effector molecules In expression of the antimicrobial activity of macrophages against Mycobacterium avium complex: roles of reactive nitrogen intermediates, reactive oxygen intermediates, and free fatty acids
Authors: Akaki Tatsuya , Sato Katsumasa , Shimizu Toshiaki , Sano Chiaki , Kajitani Hiroko , Dekio Satoshi , Tomioka Haruaki 
Published: January 2018

Abstract
We studied microbicidal activities of reactive nitrogen intermediates (RNI), free fatty acids (FFA), and reactive oxygen intermediates (ROI) against Mycobacterium aviumcomplex (MAC) and the mode of macrophage (mΦ) production of these effectors. (1) Intracellular growth of MAC in murine peritoneal mΦs was accelerated by scavengers for ROI or RNI and inhibitors of nitric oxide synthase or phospholipase A2, indicating roles of ROI, RNI, and FFA in mΦ anti-MAC functions. (2) Acidified NaNO2-derived RNI, FFA (linolenic and arachidonic acids), and the H2O2-mediated halogenation system exhibited a significant anti-MAC bactericidal activity. The combination of RNI with FFA showed a synergistic effect However, the H2O2-halogenation system in combination with either RNI or FFA showed an antagonism. When Listeria monocytogenes(Lm) was used as a target organism, the combinations of RNI + FFA and RNI + H2O2-halogenation gave a synergistic effect, whereas FFA + H2O2-halogenation showed an antagonism in exerting bactericidal activity. In addition, when ROI generated by the xanthine oxidase-acetaldehyde system was combined with RNI, anti-Lm but not anti-MAC activity was potentiated. (3) ROI production by murine peritoneal mΦs was observed immediately after contact with MAC organisms (MAC stimulation) and ceased within 2 h. FFA release was seen 1-24 h after MAC stimulation. RNI production was initiated from 3 h and increased during the first 36 h and continued at least for 4 days. These findings suggest that RNI and FFA rather than ROI are important effectors of anti-MAC functions of mΦs, and the collaborating action of RNI with FFA temporarily participates in mΦ-mediated killing of MAC in the relatively early phase after MAC stimulation.
Bacterial LPS and IFN-γ trigger the tyrosine phosphorylation of vav in macrophages: evidence for involvement of the hck tyrosine kinase
Authors: English B Keith , Orlicek Shari L , Mei Zhuyong , Meals Elizabeth A 
Published: January 2018

Abstract
We and others have previously reported that tyrosine kinases play key roles in the activation of macrophages by both bacterial lipopolysaccharide (LPS) and interferon-γ (IFN-γ). However, little is known regarding the substrates of tyrosine phosphorylation that mediate macrophage activation and the resultant production of inflammatory mediators. In lymphocytes and other hematopoietic lineages, tyrosine phosphorylation of the proto-oncogene vavappears to be an essential component of cell activation. In this study, we demonstrate that both LPS and rIFN-γ trigger the prompt, dose-dependent tyrosine phosphorylation of vavin murine RAW 264.7 macrophages. In addition, vavis physically associated with the src-related kinase hckin murine macrophages, and antisense oligonucleotides specific for murine hckblock both LPS and rIFN-γ-mediated vavphosphorylation. These findings suggest that hckprobably mediates vavtyrosine phosphorylation during macrophage activation and that LPS and rIFN-γ-mediated signaling pathways partially overlap.
The cytoplasmic domains of complement regulatory protein CD46 interact with multiple kinases in macrophages
Authors: Wong Timothy C , Yant Stephen , Harder Brandon J , Korte-Sarfaty Jennifer , Hirano Akiko 
Published: January 2018

Abstract
Membrane cofactor protein (CD46), which normally protects autologous cells from complement lysis, is the human cell receptor for measles virus (MV). Interaction between MV and CD46 on monocytes can lead to suppression of monocyte activation. We have investigated the interaction between the cytoplasmic sequences of CD46 and kinases in a mouse macrophage cell line. Glutathione-S-transferase (GST) fusion proteins bearing the Cyt1 or Cyt2 alternative cytoplasmic domain of CD46 associate with macrophage kinase activity, which phosphorylates multiple proteins co-purified with the GST fusion proteins. Association with the macrophage kinase activity correlates with tyrosine phosphorylation of the CD46 cytoplasmic domains. Removing the CD46 sequences or introducing a frame-shift mutation abrogates the association with macrophage kinase activity. Renaturation studies reveal multiple kinases with apparent molecular mass of 82, 79, 58, and 50/49 kDa, which associate specifically with both CD46 cytoplasmic domains. Alanine substitutions at a juxtamembrane Tyr-X-X-Leu motif in the Cyt1 domain completely abrogate the association with macrophage kinases and tyrosine phosphorylation of Cyt1; but similar substitutions in the Cyt2 domain only partially reduce the association with kinases and tyrosine phosphorylation of Cyt2. These results reveal a specific interaction between complement regulatory protein CD46 and macrophage kinases. These findings may provide an important clue for understanding immune modulation by MV.
Selenium and vitamin E deficiency impair transferrin receptor internalization but not IL-2, IL-2 receptor, or transferrin receptor expression
Authors: Pighetti Gina M , Eskew Mary L , Reddy C Channa , Sordillo Lorraine M 
Published: January 2018

Abstract
Vitamin E and Se deficiency increase the risk of disease by impairing the immune response. To aid in the understanding of how vitamin E and Se deficiency reduce immune competence, this study examined several mechanisms necessary for lymphocyte proliferation. Weanling rats were fed a vitamin E-deficient, selenium-deficient, or control diet for 8 weeks. At this time splenic mononuclear cells were isolated and stimulated with concanavalin A for 48 h. Although the percentage of lymphocytes and monocytes capable of proliferating were consistent among the dietary groups, lymphocyte proliferation was decreased significantly in vitamin E- and selenium-deficient rats. This decrease in proliferation was not associated with alterations in interleukin-2, interleukin-2 receptor, or transferrin receptor expression. However, stimulated cells from vitamin E- and Sedeficient rats internalized few if any transferrin receptors. Reduced transferrin receptor internalization may limit lymphocyte expansion by depleting the intracellular iron stores needed for cellular function and proliferation.
Myeloid-specific gene expression
Authors: Clarke Sandra , Gordon Siamon 
Published: January 2018

Abstract
The mononuclear phagocytes are recruited from bone marrow precursors to most tissues of the body, particularly during inflammation or immune stimulation. This combination of accessibility as stem cells and heterogenity of tissue locations makes the myeloid cell potentially important as a carrier of therapeutic agents. Understanding the regulation of transcription in myeloid cells is necessary for any future design of tissue-specific gene targeting vectors, particularly if there are inherent size limitations. Identified members of the C/EBP, Runt/PEBP2/CBF, and Ets families of transcription factors are critical for myeloid-specific gene expression and may have myeloid-restricted expression or myeloid-specific regulation in the hematopoietic system. AP-1, Sp1, and Myb appear to be important for myeloid-restricted expression in some cases. In addition, factors involved in the up-regulation of the level of gene expression when macrophages are activated by agents such as interferon-γ and bacterial products have been identified. Some of the sequences to which these transcription factors bind in myeloid-restricted genes have been tested in cell lines and in transgenic mice and it is now possible to make an attempt to describe the characteristics of a myeloid-specific promoter.
CD10 inhibitors increase f-Met-Leu-Phe-induced neutrophil transmigration
Authors: Hofman Paul , Selva Eric , Le Negrate Gaëlle , d'Andrea Lisanne , Guérin Sandrine , Rossi Bernard , Auberger Patrick 
Published: January 2018

Abstract
A variety of bacterial enterocolitis in their active stages are characterized by the migration of polymorphonuclear leukocytes (PMNs) across epithelial surfaces. These mechanisms could explain some effects of enterotoxins observed in the intestinal mucosae. Here, using specific inhibitors, we investigated the potential role of CD10 (E.C. 3.4.24.11), present at the surface of human neutrophils, on formyl-Met-Leu-Phe (fMLP)-induced PMN migration across cultured monolayers of the human intestinal cell line T84. Transmigration of human neutrophils across T84 epithelial cells was observed for concentrations of fMLP as low as 10–9 M, whereas maximal effect was achieved at 10–7 M as determined by transepithelial resistances and PMN myeloperoxidase assays. RB25, a CD10 inhibitor, reduced by two orders of magnitude the concentration of fMLP required to obtain full neutrophil transmigration across T84 epithelial cell line. RB25 response was concentration dependent with half-maximal and maximal effect occurring at 10–9 and 10–7 M, respectively. These concentrations of RB25 corresponded exactly to the half-maximal and maximal inhibition of endopeptidase 24.11 at the neutrophil cell surface. However, the effect of CD10 inhibitors on PMN transmigration cannot be accounted for by a direct action on T84 epithelial cells, since these cells fail to express any detectable endopeptidase 24.11 activity. Moreover, blocking of CD10 enzymatic activity by various and selective inhibitors potentiated the effect of low concentrations of fMLP on PMN transmigration. Finally, RB25 failed to affect interleukin-8 (IL-8)-induced PMN transmigration across T84 epithelial cells, in agreement with the preference of CD10 for small peptidic substrates. Taken together, these results demonstrate that inhibition of CD10 significantly reduced the concentration of fMLP needed for eliciting transmigration of PMN across intestinal epithelia.
IL-8 is an essential mediator of the increased delayed-phase vascular permeability in LPS-induced rabbit pleurisy
Authors: Fukumoto Takumi , Matsukawa Akihiro , Yoshimura Teizo , Edamitsu Sunao , Ohkawara Susumu , Takagi Katsumasa , Yoshinaga Masaru 
Published: January 2018

Abstract
We investigated the involvement of IL-8 in the delayed vascular permeability (VP) in rabbit lipopolysaccharide (LPS)-pleurisy. Maximal level of interleukin-8 (IL-8) was detected in pleural fluid at 2 h after LPS injection and anti-IL-8 inhibited the delayed VP by 90%. Injection of homologous IL-8 induced VP, the time-course of which preceded that of LPS-induced delayed VP. Production of IL-8 in LPS-pleurisy was inhibited with anti-tumor necrosis factor α (TNF-α), whereas the production of TNF-α was not affected with anti-IL-8. Injection of IL-8 did not induce TNF-α production and anti-TNF-α had no effect on IL-8-induced VP. Injection of homologous TNF-α induced IL-8 production and VP, and TNF-α-induced delayed VP was blocked with anti-IL-8. These results indicate important roles of IL-8 in LPS-induced delayed VP and that TNF-α causes the delayed VP through the production of IL-8.
Leukocytes of the intestinal muscularis: their phenotype and isolation
Authors: Kalff Jörg C , Schwarz Nicolas T , Walgenbach Klaus J , Schraut Wolfgang H , Bauer Anthony J 
Published: January 2018

Abstract
The basal presence of immunologically potent cells within the intestinal muscularis externa and their functional significance is unclear. Our aim was to investigate the basal distribution of various leukocyte populations within the rat jejunal muscularis. In addition, we sought to immunohistochemically phenotype the muscularis macrophage in jejunal whole-mounts, isolate these cells in primary culture, and investigate their ontogenesis. Macrophages form a regularly distributed network that expresses major histocompatibility complex class II, CD14 receptors, and a low level of CD11/ CD18. The macrophages are activated by dissection and are present in fetal animals. Enriched macrophage cultures show a normal resident phenotype and remain present for weeks in dissociated muscularis cultures. The results also demonstrate the presence of neutrophils, monocytes, mast cells, and lymphocytes within the muscularis and suggest that the dense network of muscularis macrophages may be a potent resident trigger for inflammation in response to tissue injury or bacterial translocation.
Activation of cytokine production, tumoricidal properties, and tyrosine phosphorylation of MAPKs in human monocytes by a new synthetic lipopeptide, JBT3002
Authors: Dong Zhongyun , Killion Jerald J , Kumar Rakesh , Eue Ines , Yang Xiulan , Lu Weixin , Su Bing , Fidler Isaiah J 
Published: January 2018

Abstract
We investigated the expression of cytokine genes and tumoricidal properties in human blood monocytes in response to a new synthetic immunomodulating lipopeptide, JBT3002. Incubation of peripheral blood monocytes with free-form JBT3002 or JBT3002 encapsulated in multilamellar phospholipid vesicles (liposomes, MLV-JBT3002) induced tumoricidal properties in a dose-dependent manner. Both MLV-JBT3002 and free-form JBT3002 induced production of tumor necrosis factor α, interleukin-1β, and interleukin-6 in a dose-dependent manner with similar kinetics. Treatment of monocytes with interferon-γ did not significantly alter the expression of cytokine genes but increased the expression of cytokines induced by MLV-JBT3002 and free-form JBT3002. In contrast to monocyte activation by lipopolysaccharide (LPS), activation by JBT3002 was independent of serum and was not inhibited by CD14-neutralizing antibody. Incubation of monocytes with JBT3002 induced a rapid increase in tyrosine phosphorylation of proteins with apparent molecular masses of 42 and 38 kDa, a migration band shift of c-Jun NH2-terminal kinase 1 (JNK1), and activation of extracellular signaling regulated kinases. Consistent with its effect on cytokine expression, stimulation of these intracellular signaling pathways by JBT3002 was not inhibited in serum-free conditions. Collectively, the data indicate that the synthetic lipopeptide JBT3002 is a potent monocyte activator that modulates monocyte function by mechanisms similar to LPS but by a distinct receptor.
Involvement of tyrosine phosphorylation in inhibition of fMLP-induced PLD activation by N-acetyl-L-cysteine in differentiated HL60 cells
Authors: Nakamura Mitsuhiro , Nakashima Shigeru , Katagiri Yoshihiro , Nozawa Yoshinori 
Published: January 2018

Abstract
N-acetyl-L-cysteine (NAC), which is known as a multipotential agent; an antioxidant, a thiol reagent, or a tyrosine kinase inhibitor, inhibited N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced phospholipase D (PLD) activation in HL60 cells in a concentration-dependent manner (IC50 = 2 mM). Its inhibitory mechanism was examined in this study to gain insight into the regulation of PLD activity. NAC had no direct effect on membrane PLD activity in an in vitro assay system. fMLP-induced formation of inositol phosphates via phospholipase C (PLC) was not affected by the drug, suggesting that the receptor-G protein coupling was not inhibited. H2O2, which is known to induce PLD activation in several types of cells, failed to activate PLD in HL60 cells. Pretreatment of 3-amino-1,2,4-triazole (ATZ), a catalase inhibitor, did not enhance fMLP-induced PLD activation. NAC inhibited fMLP-induced tyrosine phosphorylation of several protein bands (42, 44, 64, and 138 kDa) in a concentration-dependent manner. The temporal and concentration-dependent inhibitory profiles for tyrosine phosphorylation of 64- and 138-kDa proteins were well correlated with PLD activation. However, thiol reagents, 1 mM 2,3-dimercapto-1-propanol (2,3-DMP), 1 mM dithiothreitol (DTT), and 2 mM cysteine also did not suppress protein tyrosine phosphorylation or PBut formation by fMLP. Wortmannin, a selective phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, inhibited these two tyrosine phosphorylation bands. These results suggest that NAC inhibits fMLP-induced PLD activation through blockage of protein tyrosine phosphorylation, which is located at the downstream of PI-3 kinase.
Soluble receptors in human disease
Authors: Heaney Mark L , Golde David W 
Published: January 2018

Abstract
Soluble cytokine receptors naturally arise from genes encoding membrane-bound receptors or are direct derivatives of the receptors themselves. There is mounting evidence that soluble receptors play important roles in human disease states. In many cases, soluble receptors appear to play an integral part in the dynamic interaction between ligands and their membrane-bound receptors in maintaining and restoring health after a pathological insult but, in some instances, dysregulated expression of soluble receptors can contribute to disease pathology. Nonetheless, an appreciation of the biological actions of soluble receptors, particularly as cytokine inhibitors, has led to their therapeutic use in human diseases. Although early clinical trials of soluble receptors have had unexpected toxicities, their application in medicine continues to advance and it is likely that soluble receptors will join hormones, cytokines, and growth factors as established biological therapies. J. Leukoc. Biol. 64: 135–146; 1998.
Interactive role of nitric oxide and superoxide anion in neutrophil-mediated endothelial cell injury
Authors: Kausalya Santhanam , Nath Jayasree 
Published: January 2018

Abstract
This study addresses the interactive role of nitric oxide (NO) and reactive oxygen intermediates (ROI) by direct quantitation of NO and superoxide (O2–) in human neutrophil (PMN)-endothelial cell (EC) coculture during PMN-mediated EC injury. The results directly demonstrate an inverse correlation between NO and ROI levels in PMN-EC coculture, which significantly alters the PMN-EC adhesion and PMN-mediated EC killing. N-formyl-methionyl-leucyl-phenylalanine (fMLF)-stimulated PMN adhesion to cytokine-treated EC was decreased (&gt;25%) in the presence of S-nitroso-N-penicillamine, a NO donor. NO also inhibited EC killing by stimulated PMN, suggesting its cytoprotective role. In addition, a significant decrease in NO levels was observed in the PMN-EC coculture compared with the EC cultured alone (422.45 ± 35.76 vs. 800.79 ±41.69 pmol). The reduced NO levels were restored by the addition of superoxide dismutase, a scavenger of O2–, suggesting that PMN-derived O2– is involved in the neutralization of NO in the coculture. The results indicate an inverse correlation between NO and O2– in PMN-EC interactions and suggest the need for a critical balance between these two radicals in the regulation of PMN-mediated tissue injury. J. Leukoc. Biol. 64: 185–191; 1998.