bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single exogenous stimulus activates resident rat macrophages for nitric oxide production and tumor cytotoxicity
Authors: Lavnikova Natasha , Drapier Jean-Claude , Laskin Debra L 
Published: January 2018

Abstract
Based on experiments with mouse cells, it appears that macrophage activation for cytotoxicity requires two exogenous signals. One signal primes or sensitizes the cells, while the second activates them for killing. The present studies were designed to analyze the capacity of rat macrophages to be activated for nitric oxide production and for cytotoxicity by different inflammatory stimuli. We found that both resident alveolar macrophages (AMs) and resident peritoneal macrophages (PMs) from Sprague-Dawley rats produced nitric oxide in response to relatively low doses of a single exogenous activating stimulus [interferon-γ (IFN-γ) or lipopolysac- charide (LPS)]. Resident PMs treated with either of these agents alone also exhibited nitric oxide-mediated cytotoxicity toward xenogeneic and allogeneic tumor targets. In contrast to results reported previously with both resident and elicited PMs from mice, tumor necrosis factor-α (TNF-α) exerted only a small enhancing effect on IFN-γ-induced nitric oxide production by resident rat PMs. In addition, although some level of cooperativity between IFN-γ and LPS was observed at low concentrations of LPS (&lt; 10 ng/ml), IFN-γ did not augment the effects of higher concentrations of LPS (≥10 ng/ml) on nitric oxide production by PMs. In contrast to PMs, AMs had a strong synergistic response to combinations of IFN- γ and LPS or TNF-α but also only at relatively low concentrations of IFN-γ and LPS. Furthermore, maximum nitric oxide production induced by IFN-γ in these cells could be enhanced by TNF-α or low doses of LPS. However, as observed with PMs, combinations of IFN-γ and higher doses of LPS did not significantly augment maximum nitric oxide production induced in AMs by LPS alone. Thus, our data suggest that resident rat PMs and AMs resemble elicited mouse PMs in their ability to respond to a single activating stimulus. However, PMs and in some respects AMs differ from the latter by their reduced responsiveness to combinations of activators. Taken together, our results suggest that two exogenous stimuli are not required for full activation of resident macrophages from Sprague-Dawley rats.
Antirheumatic gold compounds and penicillamine enhance protein kinase C-mediated activation of the arachidonate- mobilizing phospholipase A2 in mouse macrophages
Authors: Bondeson Jan , Sundler Roger 
Published: January 2018

Abstract
The effects of antirheumatic gold compounds and D-penicillamine on protein kinase C- and Ca2+- mediated activation of arachidonate mobilization and the formation of eicosanoids in mouse macrophages have been investigated. Auranofin (0.2-2 μΜ) enhanced the response to phorbol ester two- to three-fold, and similar enhancement was caused by aurothiomalate, aurothioglu- cose, and penicillamine, but only after pretreatment for 1-4 h. The enhanced mobilization of arachidonate was accompanied by increased formation and release of prostaglandin E2 and 6-keto prostaglandin Flα, but not of lipoxygenase metabolites. No such enhancement occurred when the arachidonate-mobilizing phospholipase A2 was activated directly (calcium ionophore A23187). Instead, auranofin caused selective inhibition of calcium ionophore-induced formation of leukotriene C4. Treatment of macrophages with 4β-phorbol 12-myristate 13-acetate causes a rapid increase in the phosphorylation and a 1.4-1.8-fold increase in the activity of the 85-kd arachidonate-mobilizing phospholipase A2 as determined in an in vitro assay. The increase in activity was further enhanced by both the gold compounds and penicillamine. These findings indicate that the target for the enhancing effect of the antirheumatic drugs is located between protein kinase C and phospholipase A2 in the signal chain leading to activation of the latter enzyme.
Transforming growth factor β1 regulation of macrophage activation depends on the triggering stimulus
Authors: Corradin Sally Betz , Buchmuller-Rouiller Yolande , Smith Josiane , Suardet Laurent , Mau§l Jacques 
Published: January 2018

Abstract
We have examined the effects of transforming growth factor β1 (TGF-β1) on the regulation of murine bone marrow-derived macrophage function. TGF-β, added simultaneously with or up to 4 h before interferon-γ (IFN-γ) plus lipopolysaccharide (LPS), inhibited macrophage leishmanicidal activity, nitrite (NO2”) production, and secretion of prostaglandin E2. In contrast, no effect of TGF-β could be demonstrated on macrophages stimulated with IFN-γ plus tumor necrosis factor-γ (TNF-γ) under the same conditions. These results suggested that TGF-β inhibited LPS-induced triggering of macrophage activation, which was confirmed by studies with IFN- γ-primed cells. Interestingly, when macrophages were pretreated with TGF-β for 24 h, NO2− production in response to IFN-γ plus TNF-α was also inhibited. Although control and IFN-γ/LPS-stimulated macrophages were found to secrete latent TGF-β, only the IFN- γ/LPS cultures produced biologically active TGF-β. Significantly, active TGF-β was present at concentrations shown earlier to inhibit macrophage function.
Random depletion of T cells that bear specific T cell receptor Vβ sequences in AIDS patients
Authors: Boldt-Houle Deborah M , Rinaldo Charles R , Ehrlich Garth D 
Published: January 2018

Abstract
A cross-sectional PCR analysis of the TCR Vβ repertoires in HIV-1 seronegative controls and HIV-1 infected individuals with either clinically or immunologically defined AIDS [1] was performed to examine the proposed superantigen model for HIV-1 pathogenesis. In contrast to previous reports, we find neither uniform specific losses nor uniform clonal expansions of particular TCR Vβ gene families in subjects with AIDS. Instead our study, which was designed specifically to qualitatively determine the presence or absence of TCR Vβ families in both subject populations, indicates an overall diminution in the expression of TCR Vβ gene families in HIV-1 infected individuals with AIDS compared with controls. This is commensurate with the decrease in CD4 T cells in the AIDS population. Our data are therefore not directly suggestive of a common superantigen model of HIV-1 induced T cell clonal depletion or anergy, but instead emphasize a broad decrease in signals throughout the TCR Vβ repertoire in AIDS versus control groups. This random depletion in the TCR Vβ repertoire is most likely caused by aspects of HIV-1 pathogenesis other than virus- encoded superantigens.
Flow cytometric analysis of the cytotoxic effects of Actinobacillus actinomycetemcomitans leukotoxin on human natural killer cells
Authors: Shenker Bruce J , Vitale Laura A , Keiba Irene , Harrison Gerald , Berthold Peter , Golub Ellis , Lally Edward T 
Published: January 2018

Abstract
The goal of this investigation was to determine if human natural killer (NK) cells were susceptible to the cytolytic effects of the Actinobacillus actinomycetemcomitans leukotoxin (LTX). Following treatment with LTX (0–200 ng/ml), NK cell activation by interleukin-2 (IL-2) was evaluated. LTX inhibited the IL-2-induced expression of both CD69 and the IL-2 receptor. Furthermore, the up-regulation of CD56 was also impaired. To determine whether the observed functional deficits were the result of cell death, NK cell viability was evaluated by flow cytometry. Changes in forward and side light scatter patterns consistent with cell death were observed within 60 min. Direct analysis of cell viability by measuring propidium iodide exclusion, however, indicated little change in the viability of LTX-treated NK cells. Electron microscopic analysis of NK cells exposed to LTX revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation, and condensation of nucleoplasm. However, no change in membrane integrity was initially noted. Finally, LTX caused a rapid and sustained elevation in the intracellular levels of Ca2+. These morphological and biochemical changes are consistent with the notion of programmed cell death. J. Leukoc. Biol. 55: 153–160; 1994.
Elimination of macrophages by liposome-encapsulated dichloromethylene diphosphonate suppresses the endotoxin-induced priming of Kupffer cells
Authors: Bautista Abraham P , Skrepnik Nebosja , Niesman Michael R , Bagby Gregory J 
Published: January 2018

Abstract
This study was performed to elucidate the role of Kupffer cells during endotoxemia by assessing the consequences of macrophage depletion by liposome-encapsulated dichloromethylene diphosphonate (L-DMDP) following lipopolysaccharide (LPS) treatment. Results show that more than 90% of the largest Kupffer cells, arbitrarily termed KC3, were eliminated, while only 50% of the smaller Kupffer cells were depleted. The selective elimination of a subpopulation of Kupffer cells was accompanied by a significant attenuation of endotoxin (LPS)-induced serum tumor necrosis factor activity by almost 90%. Hepatic sequestration of neutrophils into the liver after LPS injection was not altered by L-DMDP. The priming action of LPS on superoxide release by neutrophils recovered from the liver in response to in vitro PMA or zymosan was not altered by L-DMDP. However, the LPS-induced priming of superoxide formation in vitro by Kupffer cells, particularly KC3, was significantly attenuated. These results indicate that selective elimination of a subpopulation of Kupffer cells by L-DMDP down-regulates the LPS-induced cytokine release in vivo and endotoxin-mediated priming of hepatic macrophages for enhanced formation of toxic oxygen metabolites. However, biological activities of neutrophils (i.e., superoxide release and hepatic sequestration) are not altered by L-DMDP, further emphasizing the specificity of L-DMDP action on Kupffer cells. J. Leukoc. Biol. 55: 321–327; 1994.
Thymic peptide modulates glutathione redox cycle and antioxidant enzymes in macrophages
Authors: Sil Park Choon , Li Lin , Lau Benjamin H S 
Published: January 2018

Abstract
The effect of a 6-kDa thymic peptide (TP) on the oxidative burst of the murine macrophage cell line J774 was determined. TP was incubated with J774 cells at 37° and 5% CO2 for 18 h, oxidative burst was triggered by zymosan, and chemiluminescence was amplified by luminol and measured in an automated luminometer. TP exhibited a concentration-dependent suppression of oxidative burst. To study the mechanisms involved in TP’s suppression of oxidative burst, its effect on the glutathione redox cycle and antioxidant enzymes was investigated. J774 cells were incubated with varying concentrations of TP for 18 h, washed, resuspended in phosphate-buffered saline, and sonicated to obtain cell lysate. Biochemical assays were performed with the lysate. TP was shown to increase the level of glutathione, and activities of glutathione-peroxidase and glutathione-reductase, indicating its ability to modulate the glutathione redox cycle. The activity of antioxidant enzyme superoxide dismutase was enhanced significantly by TP treatment while catalase activity remained unaffected. These results suggest that TP possesses an antioxidant property and therefore may be involved in the regulation of free radical mediated reactions. J. Leukoc. Biol. 55: 496–500; 1994.
HOCI production by human neutrophils activated by surface-associated IgG: Requirement for influx of extracellular calcium
Authors: Blackburn Warren D , Chatham W Winn 
Published: January 2018

Abstract
Neutrophils produce large quantities of HOCI when stimulated by surface-associated immunoglobulin G, a result not seen when neutrophils are stimulated with soluble complexes of IgG. Compared with unactivated cells or cells stimulated with soluble aggregates of IgG, a significant influx of extracellular 45Ca2+ was observed in cells activated by surface-associated IgG. Removal of extracellular calcium with EGTA almost completely blocked HOCI production. Similarly, treatment of neutrophils with lanthanum, which has been shown to interfere with calcium channels, also effectively blocked HOCI production. These results were not secondary to an overall decrease in activation, as superoxide production and release of the specific granule protein lactoferrin and the azurophilic granule protein myeloperoxidase were not significantly altered by lanthanum or EGTA. Production of H2O2, the precursor of HOCI, was similarly decreased by both EGTA and lanthanum. Induction of extracellular calcium influx with a calcium ionophore in the presence of soluble aggregates of IgG resulted in HOCI production. Production of HOCI is not sensitive to inhibition by pretreatment of cells with pertussis toxin. These observations indicate that the differences in the biological responses of human neutrophils to surface-associated IgG compared with soluble aggregates of IgG are associated with differing signaling events, including influx of extracellular calcium. J. Leukoc. Biol. 55: 793–797; 1994.
Phenotypic and functional activation of monocytes in HIV-1 infection: interactions with neural cells
Authors: Birdsall Holly H , Trial JoAnn , Hallum Jennifer A , de Jong Andrew L , Green Linda K , Bandres Juan C , Smole Sandra C , Laughter Arline H , Rossen Roger D 
Published: January 2018

Abstract
To investigate mechanisms that facilitate transendothelial migration of HIV-infected leukocytes and their interactions with neural tissues early in the disease, we studied peripheral blood from Centers for Disease Control class A patients. Patients’ monocytes displayed increased quantities of the adhesion molecules CD11a, CD11b, and very late antigen 4 (VLA-4). Expression of these correlated directly with the numbers of monocytes that migrated through confluent endothelium. These ligands also mediated leukocyte interactions with cultured human neural cell lines. Although patients’ cells bound in greater numbers, there was no evidence of target cell injury. To evaluate the direct effect of HIV-1 on monocyte neuroadhesion, we compared infected with uninfected monocytoid (U-937,THP-1) and T lymphoblastoid (MT-4) cell lines. HIV infection increased the neuroadhesiveness of monocytoid lines only. By using lines with more than 95% HIV-infected cells, we demonstrated that HIV-1 gp120 participates with lymphocyte function-associated antigen 1 and VLA-4 to mediate monocyte-neural cell interactions. J. Leukoc. Biol. 56: 310–317; 1994.
IL-4 and IL-13 have overlapping but distinct effects on HIV production in monocytes
Authors: Mikovits Judy A , Meyers Anne M , Ortaldo John R , Minty Adrian , Caput Daniel , Ferrara Pascual , Ruscetti Francis W 
Published: January 2018

Abstract
In HIV-1-infected monocytes and monocytoid cell lines, viral expression can be observed as high-level production, restricted (chronic low-level) expression, and latency (no viral expression). Interleukin-13 (IL-13) and IL-4, which have remarkedly similar deactivating effects on inflammatory monocyte functions, were studied for their regulation of HIV expression in monocytes. Pretreatment of peripheral monocytes for 48–72 h with IL-13 markedly decreased acute HIV infection, whereas IL-4 increased it. Similar effects were seen when the U1 and R-THP-1 monocytoid cell lines with restricted HIV expression were treated with these cytokines. However, when these continuously producing cell lines were chronically treated with cytokines, IL-13 increased HIV production. Neither IL-4 nor IL-13 stimulated HIV expression in latently infected cells. In chronically infected cells, several cytokines reduced viral mRNA. Both IL-4 and IL-13 increased monocyte aggregate formation, but only IL-4 ultimately stimulated cytolysis of HIV-infected monocytes as well as increased apoptosis of U1. In the presence of tumor necrosis factor α or IL-6, which upregulate HIV expression, IL-13 could no longer suppress HIV expression. These results indicate that IL-4 and IL-13, although closely related in modulating monocyte function, can have divergent effects on HIV expression in monocytes. Collectively, these data suggest that there exists a complex cytokine tissue environment with positive regulators of HIV expression able to override negative regulators. J. Leukoc. Biol. 56: 340–346; 1994.
Pasteurella haemolytica leukotoxin—induced synthesis of eicosanoids by bovine neutrophils in vitro
Authors: Clinkenbeard Kenneth D , Clarke Cyril R , Hague Christinia M , Clinkenbeard Patricia , Srikumaran S , Morton Rebecca J 
Published: January 2018

Abstract
Exposure of isolated bovine neutrophils to partially purified Pasteurella haemolytica leukotoxin caused increased synthesis of leukotriene B4 (LTB4) but not thromboxane B2 (TXB2) from endogenous arachidonic acid. Synthesis of LTB4 was closely correlated with leukotoxin-induced neutrophil lysis. At low toxin concentrations, LTB4 production lagged behind leukotoxin-induced neutrophil lysis over a 3-h period. The neutralizing monoclonal antileukotoxin antibody MM601 neutralized both leukotoxin-induced neutrophil lysis and LTB4 synthesis. Both leukotoxin-induced neutrophil lysis and LTB4 synthesis were Ca2+-devendent. When leukotoxin-induced LTB4 synthesis from exogenous arachidonic acid was examined, significant LTB4 synthesis occurred at 5 min of leukotoxin exposure, which was before leukotoxin-induced lysis developed. Leukotoxin-induced LTB4 synthesis from endogenous arachidonic acid appears to require leukotoxin-induced plasma membrane damage (occurring during neutrophil lysis), whereas LTB4 synthesis from exogenous arachidonic acid is initiated rapidly and occurs in the absence of plasma membrane damage. J. Leukoc. Biol. 56: 644–649; 1994.
Surface IgM-stimulated proliferation, inositol phospholipid hydrolysis, Ca2+ flux, and tyrosine phosphorylation are not altered in B cells from p59fyn-/- mice
Authors: Sillman Amy L , Monroe John G 
Published: January 2018

Abstract
The surface immunoglobulin M (sIgM)-associated src family protein tyrosine kinases (PTKs) p55blk, p59fyn, and p53/56lyn become activated in B cells within seconds following sIgM cross-linking. Studies using protein tyrosine kinase (PTK) inhibitors have demonstrated that PTK activity is crucial for downstream events such as calcium flux, inositol phospholipid hydrolysis, and cell cycle entry. The roles that the individual src family PTKs play in sIgM signaling are largely unknown, however. In order to determine whether p59fyn plays a distinct role in sIgM signal transduction, the signaling capabilities of B cells isolated from fyn “knockout” mice were evaluated. We observed that in the absence of p59fyn, there was no demonstrable compromise of the slgM-coupled signaling events measured (tyrosine phosphorylation, inositol phospholipid hydrolysis, and Ca2+ flux). We propose that either p59fyn is not involved in coupling sIgM to these specific signaling pathways or that other PTKs are able to compensate for the absence of p59fyn, indicating redundancy in the sIgM signaling pathways. J. Leukoc. Biol. 56: 812–816; 1994.
Review of the macrophage disappearance reaction
Authors: Barth Malcolm W , Hendrzak Jill A , Melnicoff Meryle J , Morahan Page S 
Published: January 2018

Abstract
Macrophages (Mφs) undergo a physiological response known as the macrophage disappearance reaction (MDR) in response to certain stimuli in the peritoneal compartment. The types of stimuli that can cause the MDR, the relationship of the MDR to the host immunological response, and the possible role of the MDR in Mφ activation are reviewed. The data indicate that the MDR occurs in response to both acute nonspecific inflammatory and specific immune delayed hypersensitivity processes and that the MDR may play an important role in Mφ activation. J. Leukoc. Biol. 57: 361–367; 1995.
Cloning and characterization of a novel cDNA that is IFN-γ-induced in mouse peritoneal macrophages and encodes a putative GTP-binding protein
Authors: Lafuse William P , Brown David , Castle Lynn , Zwilling Bruce S 
Published: January 2018

Abstract
Macrophage activation by IFN-γ results in a cascade of gene expression. To identify genes activated in mouse peritoneal macrophages by IFN-γ, we created a cDNA subtraction library of IFN-γ-induced genes. We have isolated from this subtraction library a novel cDNA clone, called Mg21, whose mRNA is absent in unstimulated mouse peritoneal macrophages and is induced to high levels within 4 h following the addition of IFN-γ. Induction of Mg21 mRNA by IFN-γ occurred in the presence of cycloheximide, indicating that expression of Mg21 mRNA does not require protein synthesis. A small amount of Mg21 mRNA was also induced by LPS, but not by IL-2, IL-4, IL-10, or TNF-α. The DNA sequence of Mg21 is 1617 nucleotides and contains an open reading frame that codes for a protein of 415 amino acids with a predicted molecular weight of 47,106 Da. The predicted amino acid sequence lacks a signal sequence or transmembrane segments, indicating that the protein is an intracellular protein. Computer search of the GenBank and EMBL databases indicates that this cDNA clone is unique but has 57% sequence identity with IRG-47, which is a mouse gene induced by IFN-γ in pre-B and B lymphocyte cell lines. IRG-47 encodes an intracellular protein that contains three conserved protein motifs present in GTP-binding proteins. Analysis of the protein sequence of Mg21 showed that these three conserved protein motifs are also present in Mg21. J. Leukoc. Biol. 57: 477–483; 1995.
Lipopolysaccharide modulation of a CD14-like molecule on porcine alveolar macrophages
Authors: Kielian Tammy L , Ross Christopher R , McVey D Scott , Chapes Stephen K , Blecha Frank 
Published: January 2018

Abstract
Cluster of differentiation antigen 14 (GD14) functions as a receptor for lipopolysaccharide (LPS) LPS-binding protein (LBP) complexes. Because LPS has varying effects on CD14 expression in vitro, we evaluated GDI 4 expression in response to LPS with a fully differen tiated macrophage phenotype, the alveolar macrophage. By using flow microfluorometric analysis and a radioim munoassay with an anti-human CD14 monoclonal anti body (My4) that cross-reacts with porcine GD14, we found that macrophages stimulated with LPS for 24 h ex hibited a two- to fivefold increase in CD14-like antigen compared with unstimulated cells. At low concentrations of LPS, up-regulation of the CD14-like antigen was de pendent on scrum; at higher concentrations of LPS, se rum was not required. In the absence of serum a 10-fold higher dose of LPS (10 ng/ml) was required to increase CD14-like expression. In addition, LPS-induced CD14-like up-regulation correlated with secretion of tumor necrosis factor-α, regardless of serum concentration. Blockade with My4 antibody significantly inhibited LPS-induced tumor necrosis factor-α secretion at 1 ng/ml of LPS. However, inhibition decreased as we increased the LPS concentration, suggesting the existence of GDI4-independent pathways of macrophage activation in response to LPS. Alternatively, My4 may have a lower affinity for the porcine CD14 antigen than LPS, which may have only partially blocked the LPS-LBP binding site at high concentrations of LPS. Therefore, these data suggest that LPS activation of porcine alveolar macro phages for 24 h increased CD14-like receptor expression. The degree of CD14-like up-regulation was related to LPS concentration, however, activation did not require the presence of serum at high concentrations of LPS. J. Leukoc. Biol. 57: 581–586; 1995.