bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of oxidative stress in disease progression in individuals infected by the human immunodeficiency virus
Authors: Baruchel Sylvain , Wainberg Mark A 
Published: January 2018

Abstract
This review describes the potential role of oxidative stress as a cofactor of disease progression from asymptomatic human immunodeficiency virus (HIV) infection to the acquired immunodeficiency syndrome (AIDS). Oxidative stress is a known activator of HIV replication in vitro through the activation of a factor that binds to a DNA-binding protein, NF-B, which in turn stimulates HIV gene expression by acting on the promoter region of the viral long terminal repeat. Tumor necrosis factor α (TNF-α), an essential cytokine produced by activated macrophages, is also involved in the activation of HIV infection through similar mechanisms. TNF-mediated cytotoxicity of cells exposed to this substance is related to the generation of intracellular hydroxyl radicals. An indirect argument in favor of the role of oxidative stress in HIV-associated disease progression is the consumption of glutathione (GSH), a major intracellular antioxidant, during HIV infection and progression. GSH is known to play a major role in regulation of T cell immune functions. Oxidative stress may also play an important role in the genesis of cellular DNA damage and, in this context, may be related to HIV-associated malignancies and disease progression. Finally, the role of antioxidants as components of therapeutic strategies to combat HIV disease progression is discussed.
Assessment of neutrophil leukocyte secretory response to fMLP in whole blood in vitro
Authors: Chadwick Vinton S , Ferry Dianne M , Butt Terence J 
Published: January 2018

Abstract
A simple, precise method has been developed for assessing neutrophil secretory responses (release of vitamin B12 binding protein from specific granules) to challenge of aliquots of whole blood with the bacterial chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Dose-response studies performed on blood from normal healthy volunteers showed higher maximal secretory responses in males than females (33.3 ± SEM 2.2 vs. 27.4 ± 2.5, P&lt;.005) a left shift in dose-response curves after feeding compared to fasting (P&lt;.005), spontaneous up-regulation of responses in blood incubated at 37° for 1 h, and marked up-regulation in response to preincubation with endotoxin. This whole blood challenge method may be used to study neutrophil responses in groups of individuals or patients without the confounding effects of changes in cell responses resulting from cell isolation procedures. The method may also be used as a bioassay for neutrophil-activating factors.
Nitric oxide production by tumor targets in response to TNF: paradoxical correlation with susceptibility to TNF-mediated cytotoxicity without direct involvement in the cytotoxic mechanism
Authors: Fast David J , Lynch Robert C , Leu Richard W 
Published: January 2018

Abstract
Tumor necrosis factor (TNF) is selectively cytotoxic for some tumor cells in vivo and in vitro. We determined whether TNF-mediated cytotoxicity for TNF-sensitive tumor targets was related to TNF-stimulated production of NO by the tumor cell itself. We found that a cell line that was sensitive to TNF-mediated cytotoxicity produced NO in response to TNF as measured by the accumulation of nitrite in the supernatants of TNF-stimulated cells. Production of NO in response to TNF was inhibited by the competitive substrate inhibitor, NG-monomethyl-l-arginine (NMMA). The kinetics of NO production in response to TNF indicated that most of the NO was produced during the first 24 h and peaked after 48 h of culture and that TNF-stimulated NO production was dose dependent. TNF-resistant cell lines produced less NO than a TNF-sensitive cell line, and the amount of nitrite produced correlated with the relative sensitivity of each cell line to TNF-mediated cytotoxicity. In addition, recombinant interferon-γ augmented the amount of NO produced in response to TNF by both sensitive and resistant cells and correspondingly enhanced the susceptibility of resistant cells to TNF cytotoxicity. Both sensitive and resistant cells were sensitive to NO, however, in that NO generated exogenously by culture in the presence of sodium nitroprusside was cytotoxic for both sensitive and resistant cells in a dose-dependent manner. We were unable, however, to demonstrate directly a role for NO in TNF-mediated cytotoxicity as NMMA- and arginine-free media provided little protection from TNF-mediated cytotoxicity. We tentatively conclude that the ability of adherent murine tumor cells to produce nitric oxide in response to TNF correlates directly with their level of sensitivity to TNF-mediated cytotoxicity, although NO thus produced appears not to be directly involved in the cytotoxic mechanism.
Relationship of large and small CD3- CD56+ lymphocytes mediating NK-associated activities
Authors: Ortaldo John R , Winkler-Pickett Robin , Kopp William , Kawasaki Akemi , Nagashima Kunio , Okumura Ko , Yagita Hideo , Bach Fritz H 
Published: January 2018

Abstract
We have defined a population of CD3-, CD56+ small lymphocytes (SLs) that exhibit the same phenotype and lytic capacity as natural killer (NK) cells. NK cells characteristically express the surface markers CD16 and CD56, mediate non–major histocompatibility complex (MHC)–restricted lysis, and have been equated with CD3- large granular lymphocytes (LGLs). In the present study we extended the observation that CD3-, CD56+ SLs can mediate NK- and antibody-dependent cellular cytotoxicity activity by studying the activation signals and lytic mechanisms that might be utilized by CD3-, CD56+ SLs in comparison to CD3- CD56+ LGLs. Our results show that CD3- SLs, similar to CD3- LGLs, exhibited activated killing in response to interleukin-2 (IL-2). In addition, after IL-2 activation, the CD3- SLs exhibited morphologic changes, including increases in size and granularity, and both morphologically and phenotypically became virtually indistinguishable from CD3- LGLs. Similar to CD3- LGLs, CD3- SLs could be directly activated by IL-2 alone to secrete significant quantities of interferon-γ (IFN-γ) and to express IL-2 receptor (IL-2R) p55. Examination of serine esterases and pore-forming protein (PFP) demonstrated that these cells exhibited a cytoplasmic distribution of perforin, which, unlike that of CD3- LGLs, was not associated with dense cytoplasmic azurophilic granules. Serine esterase levels were similar. However, after IL-2 activation PFP was concentrated in dense cytoplasmic granules, similar or identical to the situation in CD3-, CD56+ LGLs. These CD3-, CD56+ subsets appear to represent a continuum of activated cells that might represent various states of maturation of NK cells.
A simple and rapid method for isolation of eosinophilic granulocytes from human blood
Authors: Cramer Rita , Dri Pietro , Zabucchi Giuliano , Patriarca Pierluigi 
Published: January 2018

Abstract
A simple and rapid method for the purification of morphologically and functionally intact eosinophils from human blood of both normal and eosinophilic subjects is described. The method is based on a single centrifugation of total blood leukocytes suspended in Percoll with specific gravity 1.0853 g/ml, after erythrocyte removal by dextran sedimentation. The peculiarity of this isolation technique is the maintenance of strictly physiological values of pH and osmolality throughout the entire procedure. Moreover, the cells are not subjected to measures aimed at changing the physical properties of either neutrophils or eosinophils. Because of such characteristics, this isolation method could be usefully exploited for comparative studies of normal and eosinophilic nor-modense eosinophils and of neutrophils and eosinophils from the same noneosinophilic subject.
Inhibition site of dexamethasone on extravasation of polymorphonuclear leukocytes in the hamster cheek pouch microcirculation
Authors: Oda Takaharu , Katori Makoto 
Published: January 2018

Abstract
A video system was used to investigate the inhibitory effect(s) of the glucocorticoid dexamethasone (DEX) on polymorphonuclear leukocyte (PMN) extravasation in the microcirculation of hamster cheek pouch. DEX was given intraperitoneally at 0.1 or 0.3 mg/kg body weight 2 h before induction of extravasation by topical application of leukotriene B4 (LTB4) or formyl-methionyl-leucyl-phenylalanine (fMLP) on the microvasculature. The number, time course, and behavior of PMNs were examined in the following five steps of extravasation: (1) rolling on the venular endothelium, (2) adhesion on the endothelium, (3) passage between the endothelial cells, (4) staying in the venular wall, and (5) migration from the venular wall into the interstitial space. In either the presence or absence of DEX, topical application of LTB4 (15 pmol/50 μl) or fMLP (10 nmol/50 μl) caused an increase in the number of PMNs that adhered to the venules. Thus, DEX did not inhibit the adhesion of PMNs on the endothelial cells. The adhered PMNs induced by these chemoattractants became gradually smaller, finally disappearing in the vascular lumen, as observed on the monitor screen. The whole process took about 10 min. This passage of PMNs between the endothelial cells was also not inhibited by DEX, as over 90% of the adhered PMNs passed through the endothelial cells and advanced to the next step of extravasation in the presence or absence of DEX. When these chemoattractants were applied to DEX-untreated animals, the PMNs that passed through the endothelial cells stayed for about 30 min in the venular wall. Thereafter, PMNs migrated into the interstitial space. The numbers of PMNs in the interstitial space were counted at 30, 60, and 90 min after the application of chemoattractants. In the DEX-untreated animals, PMNs in the interstitial space started to appear by 30 min, and thereafter the number further increased. However, in the DEX-treated animals, the number of PMNs at 60 and 90 min was significantly suppressed. Since DEX may inhibit the synthesis and/or release of a proteinase(s) in the PMN granules, which would normally degrade the basement membrane, this inhibition may be due to the inability of PMNs to penetrate the basement membrane.
Interleukin-1β (IL-1β), IL-1 receptor antagonist, and TNFα production in whole blood
Authors: Nerad Judith L , Griffiths Jeffrey K , Jos WM , Van der Meer  , Endres Stefan , Poutsiaka Debra D , Keusch Gerald T , Bennish Michael , Salam Mohammed A , Dinarello Charles A , Cannon Joseph G 
Published: January 2018

Abstract
The ability of an individual to mount defense responses to infection depend in part on the capacity to produce cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF). The specialized equipment, labor intensity, and sterile practice required for the standard in vitro evaluation of cytokine production can make such evaluation impractical in some clinical situations. We report a method for stimulating whole blood to produce cytokines that can be implemented in laboratories without tissue culture facilities and requires minimal sample preparation. IL-1β and TNFβ production in whole blood samples was stimulated with endotoxin and/or phyto- hemagglutinin in standard EDTA-containing vacuum collection tubes. After incubation, plasma was removed and frozen for later assay. Comparison of this whole blood method with isolated mononuclear cell cultures indicated a significant correlation for IL-1β production (r = 0.746, β = 0.005). This technique also produced the newly described cytokine, IL-1 receptor antagonist. We conclude that the whole blood method is an acceptable alternative to isolated cell culture methods for measuring IL-1β in situations that preclude the standard in vitro approach.
Expression and complex assembly of calcium-binding proteins MRP8 and MRP14 during differentiation of murine myelomonocytic cells
Authors: Goebeler Matthias , Roth Johannes , Henseleit Ute , Sunderkotter Cord , Sorg Clemens 
Published: January 2018

Abstract
In the present study we analyzed expression and biochemical properties of the two recently cloned calcium-binding proteins MRP8 and MRP14, both members of the S-100 family, in murine myelomonocytic cells. Expression of MRPs was found to be restricted to granulocytes and distinct stages of macrophage differentiation when compared to the expression of other markers (Mac-1, F4/80) in transformed macrophage cell lines (Ml, RMB.TG, WEHI.TG, J774A, P388D) and resident and exudate peritoneal and tissue macrophages. Similarly, mRNA and protein levels of MRP8/MRP14 in murine bone marrow cells decreased during culture in L cell-conditioned medium. Applying a cross-linking technique, the formation of noncovalently associated heteromeric MRP8/MRP14 complexes of 25, 35, and 48 kd was demonstrated. Our data suggest that MRP8/MRP14 expression and complexation are characteristic for granulocytes and distinct stages of macrophage differentiation in mice. Analysis of the MRP8/MRP14+ phenotype of macrophages may provide further insights into the mechanisms underlying macrophage differentiation. J. Leukoc. Biol. 53: 11–18; 1993.
Characterization of interleukin-1 and interleukin-6 production by hepatic endothelial cells and macrophages
Authors: Feder Lisa S , Todaro Jeanine A , Laskin Debra L 
Published: January 2018

Abstract
Interleukin-1 (EL-1) and interleukin-6 (IL-6) derived from Kupffer cells are major inducers of hepatic inflammation and the acute phase response. The present studies demonstrate that liver endothelial cells also produce significant quantities of IL-1 and IL-6, suggesting that these cells also participate in these processes. Endothelial cells and macrophages were isolated from female Sprague-Dawley rats by combined collagenase and pronase perfusion of the liver followed by centrifugal elutriation. In the absence of stimulation, endothelial cells were found to spontaneously produce IL-1 and IL-6 in a time-dependent manner, reaching maximal levels after 10 h in culture for IL-1 and 6-8 h for EL-6. The amount and kinetics of cytokine production by hepatic endothelial cells were similar to those observed with Kupffer cells. In further studies, the effects of lipo- polysaccharide (LPS), a potent liver macrophage activator and inflammatory agent, on cytokine release were analyzed. Treatment of rats with LPS resulted in a decrease in IL-1 release by both cell types compared to cells from untreated animals. In contrast, LPS treatment had no major effect on IL-6 release. We also found that both macrophages and endothelial cells could be induced to produce additional IL-1 and IL-6 by treatment with LPS in vitro, but only if they were preincubated for at least 24 h prior to stimulation with LPS and analyzed for cytokine release. These data demonstrate that liver endothelial cells, like Kupffer cells, have the capacity to produce immunoregulatory and proinfiammatory cytokines. J. Leukoc. Biol. 53: 126–132; 1993.
Cytokine mRNA expression in livers of mice infected with Listeria monocytogenes
Authors: Wagner R Doug , Czuprynski CJ 
Published: January 2018

Abstract
Temporally distinct groups of cytokine expression were observed by reverse transcription-polymerase chain reaction assay, in situ hybridization, and immuno- histochemistry in the livers of Listeria monocytogenes- infected mice. One group consisted of interferon-7 (IFN- γ), tumor necrosis factor a (TNF-α), and interleukin-10 (IL-10), for which mRNAs were induced within 1 day after challenge. A second group consisted of IL-2 and IL-4, for which mRNA was strongly expressed at 1 day but then suppressed at 3 days into the infection. Granulocyte- macrophage colony-stimulating factor (GM-CSF), IL-la, and IL-6 mRNA constituted a third group, which was increased at 3 days after challenge. Distributions of cytokine mRNA-expressing cells in the liver was observed by in situ hybridization. Cells expressing TNF-α and IL-lα mRNA were present throughout liver granulomas, whereas cells that expressed IFN-γ mRNA were observed mostly along the periphery of granulomas. Cells expressing IL-2, IL-4, IL-6, IL-10, and GM-CSF mRNA were distributed principally in the hepatic sinuses. Cells expressing IL-10 mRNA increased in number early in the infection when L. monocytogenes was multiplying in the liver. We conclude that cytokine mRNA expression during the early phases of L. monocytogenes infection in mice is temporally regulated and that IFN-7, TNF-α, and IL-lα are expressed by cells associated with hepatic granulomas. J. Leukoc. Biol. 53: 525–531; 1993.
Up-regulation of neutral endopeptidase (CALLA) in human neutrophils by granulocyte-macrophage colony-stimulating factor
Authors: Connelly Jon C , Chambless Robin , Holiday David , Chittenden Kim , Johnson Alice R 
Published: January 2018

Abstract
Neutral endopeptidase 24.11 (NEP/CALLA/ CD10), an enzyme expressed on early lymphoid progenitors, neutrophils, and various other cell types, inactivates many biologically active peptides, including the bacterial chemo- tactic peptide M-formylmethionyl-leucyl-phenylalanine (fMLP). Inhibition of CD10/NEP on the surface of human neutrophils (PMNs) in vitro inhibits migration toward this chemotaxin, suggesting that enzymatic inactivation by NEP regulates the neutrophil response to fMLP. Because PMNs in inflammatory sites are exposed to various cytokines, we evaluated the effects of selected cytokines on CD10/NEP activity in vitro. Of five cytokines tested—interleukin-1 (IL-1), IL-6, and IL-8, granulocyte colony-stimulating factor, and granulocyte- macrophage colony-stimulating factor (GM-CSF) —GM- CSF provided the most consistent increase in surface NEP activity. Low concentrations (10−9-10−7 M) of GM- CSF increased NEP activity in a time- and concentration- dependent manner to more than 225% that of control (phosphate-buffered saline-treated) cells. Cytofluorome- try of cells stained with a fluorescent antibody to CD10 indicated that GM-CSF increased expression of surface CD10/NEP antigen in a similar manner. The effect of GM-CSF on NEP activity was enhanced still further by simultaneous exposure to IL-1, suggesting that combinations of cytokines may direct and regulate the neutrophil response within an inflammatory site. Rapid up- regulation of CD10/NEP underscores the importance of this enzyme for control of peptide mediators of inflammation. J. Leukoc. Biol. 53: 685–690; 1993.
TGF-beta1 inhibits both endotoxin-induced prostaglandin synthesis and expression of the TIS10/prostaglandin synthase 2 gene in murine macrophages
Authors: Reddy Srinivasa T , Gilbert Rebecca S , Xie Weilin , Luner Steven , Herschman Harvey R 
Published: January 2018

Abstract
Activated macrophages produce substantial quantities of paracrine mediators, including cytokines, nitric oxide, and prostaglandins. Transforming growth factor beta1 (TGF-beta) is a potent modulator of immune function. TGF-beta inhibits the cytotoxic activity of en-dotoxin/lipopolysaccharide (LPS)-activated macrophage cell lines and primary macrophage cultures, reducing their expression of cytokines and nitric oxide. In this report we demonstrate that TGF-beta also attenuates the LPS-induced synthesis and secretion of prostaglandin E2 in murine RAW 264.7 macrophage cells. Macrophage activation also induces accumulation of the recently described ligand-responsive prostaglandin synthase (PGS) TIS10/PGS-2. While TGF-beta alone has no effect on expression from the TIS10/PGS-2 gene, this cytokine inhibits LPS-induced TIS10/PGS-2 protein accumulation and synthesis, as well as LPS-induced TIS10/PGS-2 message accumulation in RAW 264.7 cells. TGF-beta concentrations in the range of 0.1–1.0 ng/ml (4–40 pM) maximally inhibit LPS-induced TIS10/PGS-2 message accumulation. In contrast, neither LPS nor TGF-beta has any effect on the level of PGS-1 (EG 1.14.99.1) message. TGF-beta also attenuates LPS-induced accumulation of unspliced TIS10/PGS-2 transcripts in RAW 264.7 cells, suggesting that this cytokine exerts its effects on TIS10/PGS-2 expression at the transcriptional level. TGF-beta inhibits the LPS-induced accumulation of TIS10/PGS-2 protein and message in cultured murine peritoneal macrophages, as well as in macrophage cell lines. J. Leukoc. Biol. 55: 192–200; 1994.
Involvement of CD4 in interleukin-6 secretion by U937 monocytic cells stimulated with the lectin jacalin
Authors: Taimi Mohammed , Dornand Jacques , Nicolas Michel , Marti Jacques , Favero Jean 
Published: January 2018

Abstract
The lectin jacalin is mitogenic for CD4 expressing T lymphocytes, interacts with the CD4 molecule, and inhibits HIV infection of CD4+ cells. In the present study the effect of jacalin was tested on cells from the monocyte/macrophage lineage that also express the CD4 molecule. We used CD4+ promyelomonocytic U937 cells differentiated towards the monocytic/macrophage lineage with either a mixture of two physiological agents, retinoic acid (RA) and 1α,25-dihydroxyvitamin D3 (VD), or the exogenous drug phorbol myristate acetate (PMA). The cells resulting from these treatments differed in term of CD4 expression. We focused our attention on interleukin-6 (IL-6) production, which implies an activation of the cells differentiated along both pathways. In CD4+ RA/VD-treated cells, jacalin induced a 10-fold higher IL-6 secretion than did lipopolysaccharide (LPS). This jacalin-induced IL-6 production was inhibited by agents interacting with CD4 (anti-CD4 mAbs and HIV recombinant gp120) or by recombinant soluble CD4. In contrast, the CD4- PMA-differentiated U937 cells did not secrete any IL-6 upon jacalin treatment, while they demonstrated a response to LPS similar to that of the RA/VD-differentiated cells. Together with the fact that jacalin interacts with CD4, these results provide evidence of the involvement of a CD4 dependent pathway in IL-6 production. J. Leukoc. Biol. 55: 214–220; 1994.
Interleukin-12
Authors: Brunda Michael J 
Published: January 2018

Abstract
Interleukin-12 (IL-12) is a newly characterized cytokine that has a unique heterodimeric structure. It was initially cloned from B lymphoblastoid cell lines, but the majority of IL-12 is produced by macrophages/monocytes following appropriate stimulation. IL-12 can (1) enhance the cytolytic activity of a number of effector cells including T cells, natural killer (NK) cells, lymphokine activated killer (LAK) cells, and macrophages, (2) increase proliferation of activated NK and T cells, (3) induce production of cytokines, such as interferon gamma, (4) stimulate the induction of ThI cells, (5) upregulate a number of cell surface molecules, (6) inhibit IgE secretion, and (7) act as a synergistic factor for hematopoietic stem cells. Based on these potent immunomodulatory activities, IL-12 has been evaluated in several disease models for parasitic infections and malignancies. Marked activity of IL-12 against both Lcishmania and Toxoplasma has been reported. Likewise, antimetastatic and antitumor activity, including tumor regression, has been observed against a number of murine malignancies treated with IL-12 using doses that result in little toxicity. The results suggest that IL-12 may be a useful cytokine for the treatment of a number of diseases. J. Leukoc. Biol. 55: 280–288; 1994.