bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of a prenylated 65-kd protein in macrophages by interferon or lipopolysaccharide
Authors: Vestal Deborah J , Maki Richard A , Buss Janice E 
Published: January 2018

Abstract
Treatment of murine bone marrow-derived macrophages with interferon-γ (IFN-γ) and/or lipopolysaccharide (LPS) resulted in changes in the abundance of a number of prenylated proteins. The most significant change involved a protein of 65 kd (p65) that became one of the most abundant prenylated proteins following treatment. The 65-kd protein was induced by agents that stimulate macrophage activation (IFNs or LPS) but not by cytokines that promote macrophage proliferation, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, or interleukin-3. The majority of p65 was localized to subcellular fractions containing internal and plasma membranes but was not detected in nuclear membranes. The farnesyltransferase inhibitor BZA-5B caused a dramatic decrease in p65 prenylation, suggesting that this protein may be modified by the C15 isoprenoid farnesyl. These observations provide the first direct evidence that interferons and LPS cause changes in the abundance of specific isoprenoid-modified proteins in macrophages.
Diverse immunological and hematological effects of interleukin 7: implications for clinical application
Authors: Komschlies Kristin L , Grzegorzewski Krzysztof J , Wiltrout Robert H 
Published: January 2018

Abstract
Interleukin-7 (IL-7) was originally discovered to be a pre-B cell growth factor. Soon thereafter, a broader role for IL-7 in leukocyte development and function began to be identified. IL-7 now has been shown to be a critical cytokine for normal T and B lymphopoiesis and a mobilizer of pluripotent stem cells and myeloid progenitors. IL-7 has been demonstrated to enhance T cell function and induce cytokine expression in monocytes. Preclinical studies have already found that IL-7 could accelerate murine lymphocyte regeneration following chemotherapy and bone marrow transplantation, induce anti-tumor effects in mice, and expand anti-HIV-specific human T cells. Thus it is essential that further preclinical and clinical research be performed to evaluate IL-7 as a potential therapy for leukopenia, bone marrow/stem cell transplantation, cancer, and HIV/AIDS.
An analogue of lipid A and LPS from Rhodobacter sphaeroides inhibits neutrophil responses to LPS by blocking receptor recognition of LPS and by depleting LPS-binding protein in plasma
Authors: Aida Yoshitomi , Kusumoto Keisuke , Nakatomi Kensuke , Takada Haruhiko , Pabst Michael J , Maeda Katsumasa 
Published: January 2018

Abstract
When incubated with lipopolysaccharide (LPS) in the presence of plasma, neutrophils become primed for enhanced release of superoxide in response to triggering by formyl-Met-Leu-Phe (fMLP). The effect of LPS on phagocytes is inhibited by a synthetic lipid A precursor, LA-14-PP (lipid IVa) or by LPS from Rhodobacter sphaeroides (Rs). We studied the mechanisms by which LA-14-PP or Rs-LPS inhibited LPS-induced responses. When neutrophils were exposed to LA-14-PP or Rs-LPS for 3 min and then to Escherichia coli-LPS, the antagonists inhibited priming for superoxide release, and also blocked up-regulation of CD11b and adherence. This inhibition was dependent on plasma, was not overcome by higher amounts of E. coli-LPS or plasma, and was not observed at 0°C, suggesting that E. coli-LPS was not able to interact with its receptor or other cellular recognition molecule in neutrophils that had been exposed to the antagonists. The alternative possibility that LA-14-PP or Rs-LPS depleted a plasma cofactor, resulting in inhibition of priming, was investigated by using LPS from Porphyromonas gingivalis (Pg) and Bordetella pertussis (Bp). These LPS primed neutrophils in a plasma-dependent and CD14-dependent manner, but were not blocked by LA-14-PP or Rs-LPS. When sub-optimal concentrations of plasma were exposed to LA-14-PP or Rs-LPS, and then mixed with Pg-IPS or Bp-LPS, followed by incubation with neutrophils, priming and up-regulation of GD11b were inhibited, and this inhibition was overcome by increasing the concentration of plasma. Binding of LPS-binding protein (LBP) in plasma to immobilized E. coli-LPS was inhibited by pre-incubation of plasma with LA-14-PP or Rs-LPS. Together with the result that treatment of plasma with anti-LBP antibody abolished the cofactor activity of plasma, these results indicated that LA-14-PP and Rs-LPS depleted LBP from plasma, resulting in inability of LPS to act on neutrophils. Thus LA-14-PP and Rs-LPS inhibited the action of LPS on neutrophils by at least two mechanisms, blocking of LPS receptor recognition and depletion of the cofactor LBP.
Expression and regulation of chemokines in bacterial pneumonia
Authors: Standiford Theodore J , Kunkel Steven L , Greenberger Marc J , Laichalk Lauri L , Strieter Robert M 
Published: January 2018

Abstract
Effective host defense against bacterial invasion is characterized by the vigorous recruitment and activation of inflammatory cells, which is dependent on the coordinated expression of both pro-and anti-inflammatory cytokines. In this review, we present evidence indicating that both C-X-C and C-C chemokines are integral components of antibacterial host defense. Specifically, in vitro studies indicate that C-X-C chemokines [interleukin-8 (IL-8) and macrophage inflammatory protein 2 (MIP-2)] and the C-C chemokine macrophage inflammatory protein 1 alpha (MIP-1α) augment the ability of polymorphonuclear leukocytes (PMNs) and alveolar macrophages, respectively, to phagocytose and kill Escherichia coli. In addition, the intratracheal instillation of Klebsiella pneumoniae in CD-I mice results in time-dependent production of MIP-2 and MIP-1α, and the inhibition of MIP-2 bioactivity in vivo results in decreases in lung PMN influx, impaired bacterial clearance, and early mortality. Finally, the anti-inflammatory cytokine interleukin-10 (IL-10) is also expressed within the lung during the evolution of Klebsiella pneumonia, and neutralization of IL-10 in vivo results in enhanced proinflammatory cytokine production, bacterial clearance, and increases in both short- and long-term survival. In conclusion, our studies indicate that specific chemokines are important mediators of leukocyte recruitment and/or activation in bacterial pneumonia and that the expression of these chemokines is regulated by endogenously produced IL-10.
Rapid killing of human neutrophils by the potent activator phorbol 12-myristate 13-acetate (PMA) accompanied by changes different from typical apoptosis or necrosis
Authors: Takei Hiroshi , Araki Akemi , Watanabe Hiroshi , Ichinose Akitada , Sendo Fujiro 
Published: January 2018

Abstract
To elucidate the relationship between activation of neutrophils and their subsequent death, the effect of phorbol 12-myristate 13-acetate (PMA), a potent activator of neutrophils, was examined. PMA-treated neutrophils showed morphological changes quite different from those of typical apoptosis or necrosis. After fusion of the lobate nucleus, nuclear contents of chromatin uniformly decreased in compactness and soon after the nuclear envelope was broken. Even at this stage, cytoplasmic organelles did not undergo degeneration. Membrane permeability began increasing at 3 h of incubation with PMA, subsequent to nuclear change. Conventional agarose gel electrophoresis and pulsed field gel electrophoresis of DNA from PMA-treated neutrophils revealed no DNA degradation products smaller than 300 kbp. PKC inhibitors, staurosporine and H-7, prevented cytotoxicity by PMA. Furthermore, antioxidants, thiourea, dimethylthiourea, pyrrolidinethiocarbamate, and N-acetyl-L-cysteine, but not superoxide dismutase, were also active in preventing PMA cytotoxicity, suggesting that cell suicide resulting from PMA treatment is due to oxygen radicals, especially the hydroxyl radical. A certain population of neutrophils phagocytosing opsonized zymosan also showed changes similar to those observed in PMA-treated cells.
Bacterial lipopolysaccharide confers resistance to G418, doxorubicin, and taxol in the murine macrophage cell line, RAW264
Authors: Sweet Matthew J , Hume David A 
Published: January 2018

Abstract
Many bacterial pathogens including Salmonella and Listeria replicate within macrophages. The susceptibility of these organisms to various antibiotics is dependent on the ability of macrophages to take up, retain, and deliver the antibiotic to the correct intracellular compartment. In this context, macrophages are known to express proteins that are involved in efflux of antibiotics and cytotoxic drugs, thereby reducing intracellular accumulation of such compounds. In our studies on the action of bacterial lipopolysaccharide (LPS) on the macrophage-like cell line, RAW264 we found that LPS treatment of these cells conferred resistance to the neomycin-related aminoglycoside G418 (geneticin). This phenotype was stable and was specific to LPS since colony-stimulating factor 1 and phorbol myristate acetate had no effect on G418 resistance. We have extended this observation to show that LPS induces transient resistance to the cytotoxic drugs taxol and doxorubicin. Macrophage resistance to cytotoxic drugs and antibiotics may have a number of important clinical consequences.
Different responses of plasma ACTH and corticosterone and of plasma interleukin-1β to single and recurrent endotoxin challenges
Authors: Mekaouche Mourad , Siaud Philippe , Givalois Laurent , Barbanel Gérard , Malaval Francis , Maurel Daniel , Assenmacher Ivan , Ixart Guy 
Published: January 2018

Abstract
In a parallel study in 10 individual rats, three time series of plasma concentrations of ACTH, corticosterone (CORT), and interleukin-1β (IL-1β) were measured before (time 0) and at intervals between 15 and 480 min following intra-arterial (i.a.) infusions of 25μg/kg lipopolysaccharide (LPS). All LPS injections were given at 9 AM. The first time series was performed on naive rats (day 1). A sequence of six daily injections (days 3–8) of the same dose of LPS followed. The post-LPS time course of the plasma ACTH, CORT and IL-1β levels were studied on days 3 (second injection) and 8 (seventh injection). The first LPS injection induced a rapid (30 min) eightfold rise in plasma ACTH and CORT, culminating in concentrations 30 times the baseline at 60 min (ACTH) and 15 times baseline at 120 min (CORT). Both hormones receded back to the initial basal level at 480 min. On the other hand, IL-1β increased slowly to peak at 13 times baseline 120 min before declining to minimal seven- to ninefold basal levels, 480 min and even 48 h post-LPS. During the second phase of the experiment starting 48 h after the initial LPS priming sequence, the ACTH and CORT responses to daily recurrent LPS injections again differed from those of IL-1β. The post-LPS time courses of the ACTH and CORT reaction displayed a typical pattern of a progressive attenuation studied at days 3 and 8. The peak amplitudes at days 3 and 8 were reduced to 60 and 10%, respectively, for ACTH, and to 85 and 45% for CORT of those observed at the first LPS test. The duration of the response (both) was also shortened from 480 min (first LPS test) to 300 min at days 3 and 8. The post-LPS patterns of the IL-1β responses were characterized, first by basal levels seven to nine times higher than the initial baseline values (day 1), and by a rapid suppression of the post-LPS response, with only a slight (30%) increase at day 3 and no increase at day 8. Thus, after both acute and recurrent LPS administration, ACTH/CORT and IL-1β reacted differently to the endotoxin challenge. The two LPS reactive systems were not correlated. This is inconsistent with the often proposed role of increased plasma IL-1β release as an intermediary factor in the LPS-induced recruitment of the corticotropic axis in general infections.
Apoptosis of macrophages during the resolution of muscle inflammation
Authors: Tidball James G , Pierre Barbara A St 
Published: January 2018

Abstract
We tested the hypothesis that apoptosis contributes to the depletion of macrophages expressing the ED1 or ED2 antigen during the resolution of rat muscle inflammation. Muscle inflammation was induced by subjecting rat soleus muscle to 10 days of unloading followed by periods of muscle reloading. Terminal deoxynucleotidyl transferase- mediated deoxyuridine triphosphate (dUTP) labeling of apoptotic nuclei showed that apoptotic inflammatory cells increase in concentration within necrotic fibers and in the connective tissue at 2 days following muscle injury caused by increased loading. Four days following injury, the apoptotic cells within damaged fibers returned to control levels, and at 7 days following injury apoptotic cells in the connective tissue returned to control concentrations. No preferential, internucleosomal cleavage of DNA from inflamed muscle was observed, although there was greater fragmentation of DNA in inflamed muscle than in controls. Double labeling studies show that cells expressing either ED1 or ED2 antigen can undergo apoptosis in vivo. The time course of apoptosis and concentration of apoptotic cells within damaged muscle fibers indicates that apoptosis contributes to returning ED1+ cells to control concentration during the resolution of inflammation. However, apoptosis of ED2+ cells during the first week following injury is not sufficient to return ED2+ cell concentrations to control values.
Adhesion mechanisms involved in C5a-induced eosinophil homotypic aggregation
Authors: Teixeira Mauro M , Rossi Adriano G , Hellewell Paul G 
Published: January 2018

Abstract
During the process of migration into tissues, leukocytes interact primarily with vascular endothelial cells but they have also been shown to interact with each other. In this study we investigated the adhesion mechanisms involved in guinea pig eosinophil homotypic aggregation as assessed by changes in light transmission. The anti-CD18 monoclonal antibody (mAb) 6.5E, at concentrations in excess of those previously shown to abrogate CD18-dependent eosinophil adherence to serum-coated plastic, inhibited C5a-induced eosinophil aggregation to a maximum of 49–68%. In contrast, the anti-intercellular adhesion molecule-1 (ICAM-1) mAb RR1/1, which binds to guinea pig eosinophils and has been shown to block guinea pig ICAM-1 function, had no effect on C5a-induced responses. Similarly, two functionally active anti-very late antigen-4 (VLA-4) mAbs had no effect on eosinophil aggregation and did not affect the CD18-independent component of the aggregation response. The role of L-selectin in eosinophil aggregation was investigated by using heparin, the selectin-binding polysaccharide fucoidin, and the anti-L-selectin mAb MEL-14. Heparin concentration-dependently inhibited C5a- and platelet- activating factor- (PAF) induced aggregation but C5a-induced responses were inhibited more potently. Fucoidin, but not the carbohydrate dermatan sulphate, effectively inhibited C5a-induced eosinophil aggregation. PMA- and PAF-induced responses were also inhibited by fucoidin. Moreover, fucoidin and 6.5E were additive in their ability to inhibit C5a-induced aggregation. Similarly, MEL-14 effectively inhibited C5a-induced eosinophil aggregation. In conclusion, we have demonstrated that guinea pig eosinophil homotypic aggregation is mostly dependent on CD11/CD18 and L-selectin present on the eosinophil surface. In addition, VLA-4 plays no role in mediating this aggregation response.
GM-CSF and IL-3 activities in schistosomal liver granulomas are controlled by stroma-associated heparan sulfate proteoglycans
Authors: Alvarez-Silva Marcio , Borojevic Radovan 
Published: January 2018

Abstract
Connective tissue cells (myofibroblasts) from liver inflammatory granulomatous reactions to schistosome eggs are able to sustain a long-term proliferation of myeloid cells, both in vivo and in vitro. We have addressed the question of the molecular mechanisms involved in control of this extramedullar stroma-dependent production of inflammatory cells. Heparan sulfate proteoglycans (HSPGs) were purified from granuloma-derived connective tissue cells and bound to plastic or collagen substrate. Their ability to bind recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), to stimulate proliferation of the FDC-P1 myeloid cell lineage, and to modify growth factor activity was monitored. The specificity of this stroma cell-derived glycosaminoglycan interaction with the myeloid growth factors was analyzed by comparing other glycosaminoglycans and sulfated polysaccharides. HSPGs could act as an artificial myelopoietic stroma; they were both required and sufficient for binding and presenting GM-CSF and IL-3 in a biologically active form. Moreover, they were able to mediate an increase in the specific growth-promoting activity of GM-CSF and IL-3. This was specific for stroma-derived heparan sulfate and heparin, since heparan sulfate derived from other cells, other glycosaminoglycans, and related molecules had no effect. These results indicate that HSPGs can stimulate and control the in situ proliferation of myeloid cells, modifying in both quantitative and qualitative terms the composition of inflammatory cell infiltrates in hepatic granulomas.
IL-15: the role of translational regulation in their expression
Authors: Bamford R N , Battiata A P , Waldmann T A 
Published: January 2018

Abstract
We previously reported that the human T cell lymphotropic virus type I (HTLV-I)-associated adult T cell leukemia (ATL) line HuT-102 produces a cytokine designated interleukin (IL) -T. Using anti-cytokine antibodies we demonstrated that IL-T is identical to the simultaneously described IL-15. The observation of a discordance between IL-15 message expression and IL-15 synthesis led us to examine normal and aberrant IL-15 mRNA for post-transcriptional controls that inhibit protein production at the level of RNA translation. When compared to activated monocytes, IL-15 mRNA expression was 6-to 10-fold greater in HuT-102 T cells. The predominant IL-15 message from HuT-102 is a chimeric mRNA joining a segment of the R region of the long terminal repeat of HTLV-I and the 5′ untranslated region (UTR) of IL-15. R segment introduction eliminated over 200 nucleotides of IL-15 5′ UTR including 8 of 10 upstream AUGs that are present in the normal IL-15 message. On analysis of the 5′ UTR of normal IL-15, we demonstrated that these 10 upstream AUGs interfere with IL-15 mRNA translation. Thus, IL-15 synthesis by the ATL cell line HuT-102 involves an increase in IL-15 mRNA transcription and translation secondary to the production of an HTLV-I-R fusion message that lacks many upstream AUGs.
Competition between lymphocyte function-associated antigen 1 (CD11a/CD18) and Mac-1 (CD11b/CD18) for binding to intercellular adhesion molecule-1 (CD54)
Authors: Lub Marijke , van Kooyk Yvette , Figdor Carl G 
Published: January 2018

Abstract
Both human integrin receptors Mac-1 (CD11b/CD18, CR3) and lymphocyte function-associated antigen (LFA)-1 (CD11a/CD18) have been demonstrated to bind human intercellular adhesion molecule-1 (ICAM-1) (CD54). Here we show that LFA-1 and Mac-1 can bind to ICAM-1 in the mouse as well. Interestingly, we observed that binding of murine LFA-1 dominates over Mac-1 for binding to ICAM-1. Using three different murine macrophage cell lines that express distinct levels of LFA-1 and Mac-1 on their cell surface, we could only detect Mac-1-dependent adhesion to ICAM-1 when little or no LFA-1 is expressed on the cell surface. When LFA-1 and Mac-1 are expressed at similar levels, the LFA-1/ICAM-1 interaction dominates over Mac-1/ICAM-l interaction, indicating that there is a competition of LFA-1 and Mac-1 for ICAM-1 binding.
Platelets enhance Fcγ receptor-mediated phagocytosis and respiratory burst in neutrophils: the role of purinergic modulation and actin polymerization
Authors: Zalavary Stefan , Grenegård Magnus , Stendahl Olle , Bengtsson Torbjörn 
Published: January 2018

Abstract
The interaction of platelets with neutrophil granulocytes is considered to play an important role in the inflammatory process, and the present study was focused on platelet-induced modulation of Fcγy receptor-mediated functions in neutrophils. We found that phagocytosis and the respiratory burst (measured as luminol-enhanced chemiluminescence), triggered in neutrophils by immunoglobulin G (IgG)-opsonized yeast particles, were potentiated by platelets and that maximal enhancement was achieved at a physiological neutrophil/platelet ratio of about 1:50 to 1:100. Platelets both increased the intra- and extracellular generation of oxygen radicals as well as the release of myeloperoxidase from stimulated neutrophils. The presence of platelets also induced a cortical actin polymerization in neutrophils, which might explain the increased phagocytic capacity. Platelets appear to affect neutrophil function in a contact-independent manner that most likely involves ATP, indicated by the following: (1) platelet supernatants, but not fixed platelets, affected neutrophil function in the same way as viable platelets; (2) platelets raised the extracellular ATP level four- to fivefold; (3) exogenous ATP mimicked the effects of platelets on actin polymerization, phagocytosis, and the respiratory burst in neutrophils; (4) hydrolysis of extracellular ATP with apyrase or blocking of ATP receptors with suramin reversed the platelet-induced enhancement of neutrophil function. An increased accumulation of extracellular adenosine, induced by inhibiting endogenous adenosine deaminase or adding exogenous adenosine, reversed the effects of platelets. The platelet-induced potentiation of the respiratory burst was inhibited by the tyrosine kinase inhibitor genistein, suggesting that tyrosine phosphorylation is involved. However, platelets did not significantly affect the Fcγ receptor-triggered calcium response in neutrophils. In conclusion, we show that platelets, through an ATP-dependent mechanism, potentiate IgG-mediated ingestion and production of oxygen metabolites in neutrophils.
Fibronectin enhances the migration rate of human neutrophils in vitro
Authors: Everitt Elizabeth A , Malik Asrar B , Hendey Bill 
Published: January 2018

Abstract
Efficient polymorphonuclear neutrophil (PMN) migration depends on specific interactions between PMNs, endothelial cells, and extracellular matrix (ECM) proteins. We investigated the relationship between PMN migration and the ECM molecule fibronectin (FN). We used an in vitro migration assay system to show that human PMNs migrated across an FN-coated filter barrier toward a formyl-Met-Leu-Phe (fMLP) chemoattractant gradient in greater numbers than across (uncoated) bare filters. In 1 h of fMLP stimulation, 69 ± 6% of the PMNs had migrated across the FN-coated filters, whereas 46 ± 5% of PMNs migrated across bare filters. This effect was specific to FN; coating the filters with the ECM protein vitronectin did not enhance migration. Monoclonal antibodies against FN or against the α5 or β1 integrin subunits of the FN receptor inhibited the enhanced PMN migration response across FN-coated filters. These findings indicate that the extracellular matrix protein FN enhances PMN migration and that this response is mediated by the α5β1 FN receptor.