bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble TNF and membrane TNF expressed on CD4+ T lymphocytes differ In their ability to activate macrophage antileishmanial defense
Authors: Birkland Timothy P , Sypek Joseph P , Wyler David J 
Published: January 2018

Abstract
In our studies of host defense against the intracellular parasite Leishmania major, we obtained evidence for a novel mechanism of macrophage activation for antimicrobial defense that involves direct cell contact between CD4+ T lymphocytes and Leishmania-infected macrophages. The mechanism is distinctive as it does not involve secretion of lymphokines but is apparently mediated by the membrane-anchored form of tumor necrosis factor (mTNF; ~50–60 kd) present on the surface of the effector T lymphocytes. Furthermore, it is not cytotoxic to the host cell and its expression is antigen specific and genetically restricted. We prepared a Leishmania-specific cloned T-T cell hybridoma line 1B6 (CD4+ TH1) that expresses membrane-bound TNF but does not secrete TNF or other macrophage activators. We now report that 1B6 cells can activate antileishmanial defense in inflammatory macrophages, whereas soluble recombinant murine TNF (sTNF) alone is unable to do so. On the other hand, both 1B6 cells and sTNF can act synergistically with recombinant murine interferon-γ (IFN-γ, a known soluble macrophage-activating factor) in activating antimicrobial defense and NO−2 release. The effects of 1B6 alone and the synergistic effects of 1B6 and IFN-γ or sTNF and IFN-γ are arginine dependent. These results suggest that mTNF may be more efficient than sTNF in macrophage activation and that contact with effector CD4+ lymphocytes that express mTNF may be an important mechanism of host defense.
Improved chemotactic ability of neonatal polymorphonuclear cells induced by mild membrane rigidification
Authors: Wolach Baruch , Dor Michal Ben , Chomsky Ofer , Gavrieli Ronit , Shinitzky Meir 
Published: January 2018

Abstract
Membrane lipid fluidity of peripheral blood polymorphonuclear cells (PMNs) of 24 newborn infants, 2–4 days after birth, was determined by steady-state fluorescence polarization with 1,6-diphenyl 1,3,5-hexatriene (DPH) as a probe and compared with that of PMNs from 23 adults. Measurements with intact cells, which correspond to all cellular lipid domains, did not display any statistically significant difference between PMNs of the two groups. However, application of bixinoyl glucosamine, a membrane-impermeable fluorescence quencher, revealed that the PMN plasma membrane of the newborn is about 23% more fluid than that of the adult. Total cholesterol-to-phospholipid ratio of newborn PMNs was found to be lower by about 10% than that of the adult, which could account for the difference in their plasma membrane fluidity. The possible implication of this finding for the deficit in chemotactic ability of leukocytes from newborns was tested with neonatal PMNs that have incorporated cholesteryl hemisuccinate (CHS), an efficient plasma membrane rigidifier. In all neonatal PMNs tested a mild incorporation of CHS (0.5–1 min incubation in 50 μg/ml dispersion) caused a significant improvement in their net chemotaxis, from an average value of 28 ± 7 to 43 ± 11. Longer incubations with CHS caused a gradual decrease in chemotactic ability that approached the basal level after about 5 min incubation. The net chemotaxis in adult PMNs was significantly higher than that of neonatal PMNs (72 ± 13) and was gradually inhibited by incorporation of CHS without any initial augmentation. Based on these results it was estimated that about 27% of the chemotactic deficit of neonatal PMNs is mediated by their immature fluid membrane.
In vivo prenatal chlordane exposure induces development of endogenous inflammatory macrophages
Authors: Theus Sue A , Lau Karen A , Tabor Dale R , Soderberg Lee SF , Barnett John B 
Published: January 2018

Abstract
Macrophages (m⊘s), important cells in host resistance, undergo a series of biochemical changes during their progression from the resident to the fully activated stage. Both resident and inflammatory m⊘s are characterized by some unique properties. In the present study, female BALB/c mice were prenatally treated with 8 mg/kg body weight of chlordane, a cyclodiene poly-chlorinated hydrocarbon that appears to reduce immunocompetence by selectively impairing m⊘ function. Therefore, we examined functions in m⊘s from chlordane-treated mice that had been stimulated with thioglycollate. The 5'-nucleotidase activity, present in high levels in resident m⊘s but low levels in inflammatory m⊘s was elevated in resident m⊘s from vehicle-exposed animals. Conversely, inflammatory m⊘s from these animals showed significantly diminished levels of this function. Moreover, chlordane-exposed m⊘s, regardless of whether they were resident or inflammatory, exhibited decreased 5'-nucleotidase responses. When a second function, transferrin receptor binding, was analyzed, vehicle-treated inflammatory m⊘s displayed high levels of activity whereas the resident m⊘s showed very little transferrin binding. However, both resident and inflammatory m⊘s from the chlordane-exposed group demonstrated transferrin binding activity similar in magnitude to that of the vehicle-treated inflammatory m⊘s. Finally, two-dimensional polyacrylamide gel electrophoresis analysis of m⊘s from chlordane-exposed mice have characteristics of normal m⊘s that have advanced to the inflammatory stage.
A Wave of elevated intracellular free calcium spreads through human neutrophils during phagocytosis of zymosan
Authors: Schwab J Conrad , Leong Denis A , Mandell Gerald L 
Published: January 2018

Abstract
The cytosolic concentration of free calcium ([Ca2+]i) plays an important role in the control of many neutrophil functions. In this study, we characterize the early rapid subcellular changes in [Ca2+]i that occur in adherent neutrophils during phagocytosis of zymosan particles, using both dual- and single-excitation wavelength Fura-2 ratio imaging. We observed a wave of elevated cytosolic calcium that began shortly after zymosan contact and propagated from the region of neutrophil contact with the zymosan throughout the cell at a rate of ≍ 17 μm/s at 31°. The wave was initiated by both opsonized and unopsonized zymosan and occurred independently of extracellular calcium. Multiple characteristics of the [Ca2+]i signal (including the absolute and regional [Ca2+]i and wave properties such as amplitude, frequency, duration, and topography) may be responsible for the differential regulation of cellular functions in the neutrophil.
Mycobacterial Infection Primes T Cells and Macrophages for Enhanced Recruitment of Neutrophils
Authors: Appelberg Rui 
Published: January 2018

Abstract
C57BL/6 mice intraperitoneally infected with Mycobacterium bovis BCG (substrain Pasteur) recruited significantly higher numbers of neutrophils after an intraperitoneal inoculation of either BCG protein antigen or of endotoxin than uninfected control mice. Antigen-induced neutrophil recruitment was mediated by T cells of both CD4+ and CD8+ phenotype and was also observed in the C5-deficient DBA/2 mouse strain. The adoptive transfer of immune serum did not prime mice for enhanced antigen-mediated recruitment of neutrophils. The endotoxin-mediated recruitment of neutrophils was also enhanced in infected as compared to uninfected DBA/2 mice. Finally, endotoxin-pulsed purified macrophages from infected C57BL/6 mice recruited higher numbers of neutrophils than endotoxin-pulsed macrophages from normal mice in an adoptive transfer to peritoneal cavities of naive recipient mice. These data show that during mycobacterial infection, T cells and macrophages are primed for recruitment of neutrophils after being triggered in specific or nonspecific ways. This may represent a means to cope with secondary infections by allowing for extensive neutrophil infiltration readily upon microbial challenge.
Subcellular localization of heparanase in human neutrophils
Authors: Matzner Yaacov , Vlodavsky Israel , Bar-Ner Matia , Lshai-Michaeli Rivka , Tauber Alfred I 
Published: January 2018

Abstract
Abstract The subcellular localization of a heparan sulfate degrading endoglycosidase, heparanase, was studied in human neutrophils. Unstimulated cells were disrupted by nitrogen cavitation and fractionated on a Percoll density gradient into three components, separating the plasma membranes, specific granules, and azurophilic granules. Heparanase activity was measured by gel filtration analysis of 35S-labeled degradation fragments released from subendothelial extracellular matrix (ECM) or produced during incubation with soluble, ECM-derived, heparane sulfate proteoglycans. Heparanase activity was found mainly in fractions containing the specific granules; this activity was inhibited by heparin. Freezing and thawing was not needed for recovery of the enzyme from the subcellular fraction, confirming previous data about its ready release. The mechanism of the ready release of heparanase from the specific granules requires further investigation.
Interstitial pulmonary macrophages produce platelet-derived growth factor that stimulates rat lung fibroblast proliferation in vitro
Authors: Brody Arnold R , Bonner James C , Overby Lila H , Badgett Annette , Kalter Valerie , Kumar Rakesh K , Bennett Richard A 
Published: January 2018

Abstract
Alveolar macrophages from humans and several animal species produce factors in vitro that modulate fibroblast growth and have been proposed as mediators of interstitial pulmonary fibrosis. Pulmonary interstitial macrophages (IMs) have not been studied previously in this regard. Pulmonary IMs were isolated from prelavaged rat lungs by enzymatic digestion of tissue and subsequent differential adherence of cells to culture dishes. The ability of IMs to release modulators of fibroblast growth into the culture medium was assessed by measuring [3H]thymidine incorporation into DNA and/or nuclear labeling of early-passage rat lung fibroblasts exposed to medium conditioned by IMs. The percentages of nuclei labeled in fibroblast cultures exposed to interstitial macrophage–conditioned medium (IMCM) alone did not significantly differ from that observed in controls, but fibroblasts exposed to IMCM supplemented with 2% platelet-poor plasma showed a 2.6-fold increase in labeling, indicating that IMCM contains predominantly “competence” growth factor activity. Similar results were obtained using purified human platelet-derived growth factor (PDGF). The level of growth factor activity released by IMs increased in cells that had phagocytized iron spheres during the culture period. In addition, fractionation of IMCM by high-performance liquid chromatography demonstrated most of the growth factor activity at a relative molecular mass of about 35 kd. Subsequent quantitative analysis of the fractions by an enzyme immunoassay for PDGF demonstrated that IMCM contains a homologue of human PDGF. These results show that IMs are capable of producing a PDGF-like growth factor for autologous fibroblasts and that release of this factor is enhanced by exposure to an insoluble inorganic particle. Because PDGF is a potent growth factor for fibroblasts and is released by IMs, it is essential to ask in future studies whether this or similar macrophage products play a significant role in mediating fibroblast proliferation in vivo.
Two populations of splenic dendritic cells detected with M342, a new monoclonal to an intracellular antigen of interdigitating dendritic cells and some B lymphocytes
Authors: Agger Ralf , Witmer-Pack Margit , Romani Nikolaus , Stossel Hella , Swiggard William J , Metlay Joshua P , Storozynsky Eugene , Freimuth Paul , Steinman Ralph M 
Published: January 2018

Abstract
A monoclonal has been isolated that labels an intracellular antigen in dendritic cells and some B cells. The M342 hamster immunoglobulin was selected because it stained cells in the periarterial sheaths of spleen, the deep cortex of lymph node, and the thymic medulla –- the same regions in which one finds interdigitating cells, the presumptive in situ counterparts of isolated lymphoid dendritic cells. M342 labeled an antigen within granules of isolated dendritic cells, but only in cells that had been cultured for a day and not in fresh isolates. This extends recent findings that most freshly isolated spleen dendritic cells are located in the periphery of the white pulp nodule and may serve as precursors for the periarterial pool of interdigitating cells, the site for M342 staining in situ. By electron microscopic immunolabeling, the M342 antigen was found exclusively in a type of multivesicular body. M342 staining was not found in mononuclear phagocytes from blood and peritoneal cavity. Peritoneal B cells expressed M342+ granules, and upon appropriate stimulation splenic B cells developed reactive granules as well. We conclude that M342 is a strong marker for interdigitating cells. Its existence reveals intracellular specializations in the vacuolar system of antigen-presenting cells including subsets of dendritic cells.
Interactions between HIV-infected monocytes and the extracellular matrix: increased capacity of HIV-infected monocytes to adhere to and spread on extracellular matrix associated with changes in extent of virus replication and cytopathic effects in infected cells
Authors: Dhawan Subhash , Vargo Maurann , Meltzer Monte S 
Published: January 2018

Abstract
Monocytes express cell surface receptors for extracellular matrix (ECM) proteins of basement membranes. These receptors are engaged during extravasation of cells through capillary endothelium into tissue. The number of human immunodeficiency virus (HIV)-infected monocytes that adhered to ECM over 2 h was threefold higher than that of uninfected control cells. This difference was ECM specific and was not observed with a bovine serum albumin substrate. Enhanced adhesion to ECM was evident in monocytes by 4 days after HIV infection and increased through 10 days. Monocytes exposed to a T cell–tropic HIV strain that binds to but does not replicate in monocytes showed no changes in adherence to ECM. Thus, productive infection of monocytes by HIV induces a significant increase in the capacity of these cells to interact with ECM. Enhanced adhesion of HIV-infected monocytes to ECM was associated with increased spreading: at 12 h, sixfold more HIV-infected monocytes were spread on ECM than were uninfected control cells. Cell processes of HIV-infected monocytes formed a complex network on ECM: many of these cells expressed HIV proteins as detected by indirect immunofluorescence. HIV-associated cytopathic effects and levels of virion-associated reverse transcriptase activity depended on the substrate to which monocytes were attached. Virus replication and cytopathic effects in monocytes adhered to ECM, fibronectin, or plastic alone were comparable. In contrast, HIV-infected monocytes attached to laminin showed a significant increase in virus replication and in extent of cytopathic effects through 2 weeks after infection. The lowest levels of HIV replication and cytopathic effects were in monocytes attached to collagen IV. Interactions between monocytes and ECM profoundly affect the manner in which these cells control HIV infection: HIV infection changes the capacity of infected monocytes to attach and spread on ECM; attachment to ECM alters the extent of virus replication in infected cells.
Type I interferons (IFN-α and -β) suppress cytotoxin (tumor necrosis factor-α and lymphotoxin) production by mitogen-stimulated human peripheral blood mononuclear cells
Authors: Abu-khabar Khalid S , Armstrong John A , Ho Monto 
Published: January 2018

Abstract
We studied the effect of the different types of interferons on the production of cytotoxin by human peripheral blood mononuclear cells (PBMCs) stimulated with the mitogen phytohemagglutinin (PHA). Maximum secreted levels of cytotoxin were observed at day 3 in culture and consisted of both tumor necrosis factor α (TNF-α) and lymphotoxin as determined by specific antibodies. Type I interferons (IFN-α and IFN-β) consistently suppressed cytotoxin production. Both TNF-α and lymphotoxin were significantly suppressed. Mean suppression by IFN-α and IFN-β (1000 U/ml) was 56 and 66%, respectively, in PBMCs from 18 different donors. The suppressive effects of IFN-α and IFN-β on cytotoxin production were dose responsive over a range of 10 to 1000 U/ml. Type II interferon (IFN-γ) did not have consistent significant effects. Pretreatment with IFN-α or IFN-β for 24 or 48 h prior to PHA stimulation also resulted in significant suppression. Supplementation with interleukin-2 (10 U/ml) or IFN-γ (1000 U/ml) did not overcome cytotoxin suppression by IFN-α or IFN-β. Cytotoxin suppression by IFN-α and IFN-β together appeared to be noninteractive. Suppression appeared not to be due to blockade of the cytotoxin release, since both cell-associated cytotoxin and secreted cytotoxin were suppressed to the same level. These results demonstrated that cytotoxin and lymphotoxin production by PHA-stimulated PBMCs could be down-regulated by type I interferons and that there is a substantial difference between the action of type I interferons and type II interferons (IFN-γ) in modulating the biosynthesis of cytotoxins.
Interactions between HIV-infected monocytes and the extracellular matrix: HIV-infected monocytes secrete neutral metalloproteases that degrade basement membrane protein matrices
Authors: Dhawan Subhash , Toro Luis A , Jones B Eric , Meltzer Monte S 
Published: January 2018

Abstract
The frequency of human immunodeficiency virus (HIV)-infected monocytes that spread on a model basement membrane was about twofold greater than that of an equal number of uninfected control cells through the initial 12 to 18 h of culture. By 24 h, virtually all HIV-infected and uninfected control cells spread on the basement membrane gel. The frequency of spread cells in the uninfected control population was &lt; 10% of total cells by 12 days. In contrast, 30 to 40% of HIV-infected monocytes remained spread through this time interval and formed a dense interdigitated network of cell processes on and into the gel matrix. Invasion of the basement membrane matrix by HIV-infected monocytes suggested increased secretion of proteases able to digest the gel. Indeed, levels of neutral protease activity in culture fluids from HIV-infected monocytes were significantly higher than those from equal numbers of uninfected control cells. High levels of protease activity in culture fluids of HIV-infected monocytes required productive virus infection and were not observed with cells exposed to T cell-tropic HIV isolates. The predominant protease activity in these cultures was a 92-kd neutral metallogelatinase. HIV-induced changes in monocyte metalloprotease activity may be important for extravasation of infected cells to tissue or for the development of AIDS-associated neuropathology, carcinogenesis, and opportunistic infection.
Release of active oxygen radicals by leukocytes of Fanconi anemia patients
Authors: Korkina Ludmila G , Samochatova Elena V , Maschan Aleksei A , Suslova Tatjana B , Cheremisina Zinaida P , Afanas'ev Igor B 
Published: January 2018

Abstract
The release of oxygen radicals by blood and bone marrow leukocytes of patients with Fanconi anemia (FA) has been studied. It was found that the nonstimulated FA leukocytes and those stimulated by concanavalin A, SiO2, latex, and opsonized zymosan produced enhanced levels of luminol- and lucigenin-dependent chemiluminescence (CL) in comparison with normal leukocytes. At the same time, the ratio of the intensity of lucigenin-dependent CL to that of luminol-dependent CL was significantly smaller for FA leukocytes than for normal leukocytes. From these findings and from the effects of anti-oxidative enzymes and free radical scavengers on CL, it was concluded that FA leukocytes release enhanced amounts of oxygen radicals and that these free radicals contain enhanced amounts of hydroxyl or hydroxyl-like radicals more active than superoxide ion. It was proposed that elevated reactivity of the oxygen radicals released by FA leukocytes may be a major factor in the development of Fanconi anemia; this proposal is supported by the first positive results of treatment of FA patients with rutin (a nontoxic natural free radical scavenger and chelator).
Direct evidence for release of pore-forming protein during NK cellular lysis
Authors: Ortaldo John R , Winkler-Pickett Robin T , Nagashima Kunio , Yagita Hideo , Okumura Kb 
Published: January 2018

Abstract
In the present study, we have examined the exocytosis model for cellular lysis. Using monoclonal antibodies reactive with human pore-forming protein (PFP), we examined the localization of PFP at the interaction site of natural killer (NK) cells and the NK tumor targets K562 and Molt-4 as well as during antibody- dependent cellular cytotoxicity. Following the interaction of effector-target cell contact, an increased frequency of PFP was detected on the effector surface, in the micro- environment, and on the target surface of the interaction site. This temporal deposition of PFP was paralleled by loss of target cell integrity and release of chromium. In addition, selective deposition of PFP was seen at the interaction site of the target cell compared to other target cell regions. Collectively, these results are consistent with the exocytosis model and further support the hypothesis that PFP is one of the secreted moieties involved in NK cellular cytotoxicity
Transforming growth factor-β is the major mediator of natural suppressor cells derived from normal bone marrow
Authors: Moore Steven C , Shaw Michael A , Soderberg Lee S F 
Published: January 2018

Abstract
We previously reported that murine bone marrow cells activated by interleukin-3 (IL-3) or granu- locyte-macrophage colony-stimulating factor (GM-CSF) had potent nonspecific natural suppressor (NS) cell activity. In the present study, we demonstrated that these activated NS cells released a soluble factor (or factors) capable of nonspecifically inhibiting T cell mitogenic responses. Consistent with the properties of Transforming growth factor-β (7GF-β), treatment of the NS supernates with heat failed to denature the factor, and in fact significantly increased its suppressive activity. The NS suppressor factor strongly inhibited proliferation of the TGF- β-sensitive tumor cell line, A549. Cytokine activation of suppressive activity correlated with the production of a 10- to 13-kDa protein, consistent with the size of TGF-β and rIL-3 induced a sevenfold increase in TGF-β transcription. Finally, neutralizing anti-TGF-β antibody inhibited the suppressive activity of the supernates, indicating that TGF-β was responsible for most, if not all, of the suppression expressed by these bone marrow NS cells.