bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Endogenously Derived Leukotrienes in the Regulation of Lysosomal Enzyme Expression in Macrophages Exposed to β 1,3-Glucan
Authors: Lew D Betty , Leslie Christina C , Henson Peter M , Riches David W H 
Published: January 2018

Abstract
The expression of the lysosomal enzyme hexosaminidase has been shown to be stimulated by the exposure of mouse macrophages to β 1,3-glucan, a particulate component of yeast cell walls and zymosan particles. Exposure of mouse peritoneal macrophages to particulate β 1,3-glucan (100 μg/ml) was also found to stimulate the production of eicosanoids from both the cyclooxygenase (prostaglandin E2) and 5′-lipoxygenase (leukotriene C4) pathways. The objective of this study was to determine the relationship, if any, between the production of arachidonic acid metabolites and the increased expression of lysosomal enzymes. To determine if products of the cyclooxygenase or 5′-lipoxygenase pathway were involved in the regulation of hexosaminidase expression, macrophages were exposed to β 1,3-glucan in the presence of indomethacin, an inhibitor of cyclooxygenase; 4,7,10,13 ETYA, an inhibitor of both cyclooxygenase and 5′-lipoxygenase; or AA861, a selective inhibitor of 5′-lipoxygenase. While the increased expression of hexosaminidase was not affected in macrophages stimulated with β 1,3-glucan in the presence of indomethacin, both 4,7,10,13 ETYA and AA861 completely blocked the response, suggesting a role for products of the 5′-lipoxygenase pathway in the regulation of hexosaminidase expression. To further explore the relationship between arachidonate release and the increased expression of hexosaminidase, macrophages were exposed to phospholipase A2 in an attempt to circumvent the interaction between β 1,3-glucan and the macrophage membrane. Incubation with phospholipase A2 was found both to induce the accumulation of LTC4 in the culture supernatant and to stimulate the increased expression of hexosaminidase. The mechanism of regulation of hexosaminidase expression by products of the 5′-lipoxygenase pathway was investigated by incubating macrophages with purified luekotrienes in either the presence or absence of β 1,3-glucan. Incubation of macrophages with purified LTC4 or LTB4 in the absence of β 1,3-glucan failed to stimulate the expression of hexosaminidase. However, challenging macrophage monolayers with LTC4 or LTB4 in the presence of a suboptimal concentration of β 1,3-glucan (1 μg/ml) led to a synergistic increase in the expression of hexosaminidase. Collectively these data suggest that the leukotriene products of the 5′-lipoxygenase pathway, LTC4 and LTB4, regulate the expression of lysosomal enzymes by apparently priming macrophages, thereby increasing their sensitivity to triggering agents such as β 1,3-glucan. Since macrophages produce LTC4, and the increased expression of hexosaminidase is prevented by inhibitors of the 5′-lipoxygenase pathway, the data further suggest that LTC4 may prime macrophages in an autocrine or paracrine fashion.
Neutrophil Erythrotoxicity Induced by Phorbol Myristate Acetate: Mechanisms Involved in Neutrophil Activation
Authors: Geffner Jorge R , Fontán Patricia A , Sordelli Daniel O , Isturiz Martin A 
Published: January 2018

Abstract
The capacity of phorbol myristate acetate (PMA) to prime neutrophil cytotoxic responses induced by a second stimulus was investigated. Treatment of neutrophils with low concentrations of PMA (0.2–0.5 ng/ml) for 18 hr at 37°C markedly enhanced cytotoxicity triggered by Ca2+ ionophore A23187, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and PMA. Pretreatment with PMA also enabled neutrophils to mediate significant cytotoxicity when triggered by platelet-activating factor (PAF), a stimulus unable to induce untreated cells to display cytotoxicity. Conversely, neutrophil cytotoxicity triggered by immune complexes (IC) was not modified by PMA treatment, whereas cytolytic activity of neutrophils against antibody-sensitized target cells was significantly increased. Treatment with PMA concentrations higher than 1 ng/ml directly triggered neutrophil cytotoxicity. Interestingly, we found that PMA-triggered neutrophils were able to sustain maximal levels of cytotoxicity for at least 8 hr after stimulation. With regard to the mechanisms involved in neutrophil activation by PMA, we found that catalase but not superoxide dismutase (SOD) prevented neutrophil activation measured as 1) induction of cytotoxic responses, 2) increase of neutrophil adhesiveness to cell-free surfaces, and 3) inhibition of chemotactic responses to FMLP. These findings suggest that H2O2 may play a major role in neutrophil activation induced by PMA.
Selective Radiation Resistance of Immunologically Induced T Cells as the Basis for Irradiation-Induced T-Cell-Mediated Regression of Immunogenic Tumor
Authors: Dunn Pamela L , North Robert J 
Published: January 2018

Abstract
Sublethal, whole-body γ-irradiation of immunocompetent, but not T cell deficient, mice bearing an established immunogenic tumor results in T-cell-mediated complete tumor regression and in long-term host survival. This striking T-cell-dependent immunotherapeutic action of irradiation was paradoxically associated with the destruction of over 90% of host T cells and with a state of severe immunodepression as evidenced by the inability of irradiated mice to reject a tumor allograft. Furthermore, whereas exposure to 500 rads caused regression of a syngeneic tumor implanted 6 days before irradiation, it caused enhanced growth of a different syngeneic tumor growing on the same animal and implanted 1 day before. This ability of irradiation to cause regression of a 6 day tumor, but accelerated growth of a 1 day tumor, was also seen when the tumors were implanted in the reverse order. This means that, between days 1 and 6 of a tumor growth, tumor-specific T cells are converted from a radiosensitive to a highly radioresistant state, almost certainly because of having been activated and inducted into the antitumor immune response. This explanation for the selective radioresistance of effector T cells is based on publications showing that activated, in contrast to resting, T cells are highly radioresistant. Thus irradiation-induced, T-cell-mediated tumor regression depends not only on the destruction of radiosensitive suppressor T cells but also on the selective sparing of radioresistant activated effector T cells that are needed to destroy the tumor in the absence of suppression.
Cyclosporine A Induces an Early and Transient Rigidification of Lymphocyte Membranes
Authors: Niebylski Charles D , Petty Howard R 
Published: January 2018

Abstract
The effect of cyclosporine A (CsA) on peripheral blood lymphocyte (PBL) membranes was studied using fluorescence techniques. Light scattering and intercalation experiments indicate CsA has a critical micelle concentration of 3 × 10–5 M. Doses above this critical concentration were avoided during these in vitro studies. Steady-state fluorescence polarization of the lipid probe DPH in peripheral blood lymphocyte membranes revealed that 10–5 M CsA caused a significant increase in the fluorescence polarization 1–5 min after exposure (15–16% above control DPH polarization values). This initial increase in polarization plateaued at 10–11% above control values within roughly 40 min. Fluorescence lifetime measurements of DPH during this response reveal a slight increase in DPH lifetime. The increased DPH lifetimes showed that polarization measurements alone underestimate the rigidity of DPH's microenvironment. Measurements of DPH polarization and lifetime were analyzed using the Perrin equation to calculate the apparent microviscosity. Control PBL membranes at 37°C exhibited a microviscosity (η) equal to 1.89 poise (P). Five to 10 min after CsA exposure η = 2.62–2.68 P and plateaus at η = 2.31–2.51 P 20–120 min after exposure. Dose-response studies show that prolonged (&gt;90 min) exposure to CsA alters lymphocyte membrane fluidity. This early response in lymphocytes to CsA may correspond to other events associated with the initial binding of CsA to lymphocyte membranes such as membrane depolarization and alterations in phospholipid metabolism. Intravenous delivery of CsA in clinical studies has shown that a similar CsA dose of near 10–5 M is available in the blood during the first hour after injection. The evidence presented here suggests that peripheral blood lymphocyte membranes are rigidified when exposed to CsA doses similar to those found in patient's blood immediately following intravenous administration.
HIV Replication and Persistence in Human Gastrointestinal Cells Cultured In Vitro
Authors: Moyer Mary Pat , Gendelman Howard E 
Published: January 2018

Abstract
Epithelial and submucosal mesenchymal (SM) cells from normal human small intestine and colon could be directly infected by several strains of the human immunodeficiency virus (HIV). Macrophage-derived virus strains were more potent than the HTLVIIIB prototype strain. Persistent release of virus over several months implies that the human gastrointestinal tract may serve as a site for primary infection and as a reservoir for the virus. Furthermore, HIV infection of SM cells may be an in vitro model of Kaposi's sarcoma.
Inflammatory Responses to Cryptococcosis in Congenitally Athymic Mice
Authors: Salkowski Cindy A , Balish Edward 
Published: January 2018

Abstract
Histopathology revealed that nu/nu mice developed both acute and chronic inflammatory responses following infection with Cryptococcus neoformans. In comparison to inflammatory responses in nu/+ mice, the responses in nu/nu mice were delayed, less intense, contained predominantly more polymorphonuclear leukocytes (PMNs) than macrophages (Mφs), and did not develop into granulomas. In addition, nu/nu mice developed cryptococcal skin lesions demonstrating that C. neoformans is dermatotropic in a T-cell deficient host. Quantitative culturing of infected organs confirmed that delayed and incomplete inflammatory responses observed in nu/nu mice correlated with their enhanced susceptibility to C. neoformans.
T Helper/Inducer (CD4+) Cells Prestimulated With PPD Induce Monocytes to Produce Interleukin-1β
Authors: Dunlap Nancy E , Tilden Arabella B 
Published: January 2018

Abstract
We obtained peripheral blood mononuclear cells (PBMC) from four healthy, tuberculin purified protein derivative (PPD) reactive donors and cultured these cells in media containing PPD (low dose = 200 ng/ml or high dose = 1 fig/ml). Five days after the addition of PPD, T cells were isolated, washed, and added to autologous adherent cell cultures at a 1:1 ratio. Adherent cells were then cultured for 24 h in media only (baseline), media plus lipopolysaccharide (LPS, 2 μg/ml; positive control), or media containing the prestimulated T cells. After 24 h, supernatants were harvested and interleukin 1β (IL-β) levels were assayed by radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). The results show that T cells prestimulated with low dose PPD (200 μg/ml) did not induce IL-1 production by adherent cells (mean increase over baseline 0.2 ± 1.3 standard deviation [SD] ng/ml, P = 0.61). However, T cells prestimulated with high dose PPD (1 tig/ml) did induce adherent cells to secrete IL-1β (mean increase over baseline 1.7 ± 0.62 [SD] ng/ml, P = 0.01), but this induction was abolished when cell-to-cell contact was prevented by use of double well chambers (mean increase over baseline 0.1 ± 0.36 [SD] ng/ml, P = 0.69). Prestimulated T helper (CD4+) cells were able to induce monocytes to secrete IL-1β but prestimulated CD8+ T cells were not. These data suggest that when T helper (CD4+) cells are sufficiently activated they acquire the ability to induce monocytes to secrete IL-1β. Cell-to-cell contact between monocytes and T cells is required. This function of activated T cells may be important in the normal cellular immune response.
FcR-Independent Antibody-Mediated Cellular Cytotoxicity
Authors: Colsky Arthur S , Mendez Luis E , Peacock James S 
Published: January 2018

Abstract
In this study we used palmitate-derivatized antibodies (pal-Ab) to examine the minimum contribution of Fc receptors (FcR) to macrophage (Mφ)-mediated lysis and phagocytosis in antibody-dependent cellular cytotoxicity (ADCC). Pal-Ab specific for chicken erythrocytes (CE) were incorporated into the plasma membranes of Mφ by insertion of the palmitate hydrocarbon chains into the outer leaflet of the phospholipid bilayer. In this system, the palmitate anchor bypassed the requirement for FcR in antibody-dependent effector-target conjugation and provided a unique opportunity to uncouple antibody-FcR interactions in ADCC. We show that binding of CE targets by P388D1 Mφ effector cells through anti-CE pal-F(ab')2 can lead to efficient extracellular target cell lysis, but not phagocytosis. In contrast, pal-F(ab')2-mediated interactions between CE and peritoneal exudate Mφ (PEM) activated both ingestion and extracellular lysis of the targets. In normal ADCC, FcR-dependent interactions between CE and either P388D1 cells or PEM triggered both extracellular lysis and phagocytosis. Our results demonstrate that lysis and phagocytosis in CE-directed ADCC by Mφ have different minimum requirements for FcR functions. Moreover, our results suggest that FcR-independent triggers on the PEM surface are capable of triggering target cell lysis and internalization following antibody-mediated interactions.
Selective Depletion of Liver and Splenic Macrophages Using Liposomes Encapsulating the Drug Dichloromethylene Diphosphonate: Effects on Antimicrobial Resistance
Authors: Pinto Angelo J , Stewart Deneen , van Rooijen Nico , Morahan Page S 
Published: January 2018

Abstract
The current results provide direct evidence for a role of tissue macrophages (Mφ) in natural immunity and support the use of immunomodulators to enhance antiviral resistance in immunocompromised individuals. In this study, macrophages (Mφ) in the spleen and liver were eliminated by intravenous (i.v.) injection of the drug dichloromethylene diphosphonate (DMDP) encapsulated in liposomes. The effect of this depletion system on peritoneal Mφ, peripheral blood leukocytes, splenic natural killer (NK) activity, and natural and immunomodulator-induced host resistance was then assessed. Barrier-maintained CD-1 female mice were inoculated i.v. either with DMDP liposomes, free liposomes (containing no DMDP), or saline on day -2 or on days -3 and -1 before cell population analysis or infection. Single or double treatment with DMDP liposomes had no effect on peritoneal Mφ as indicated by no changes in total number, differential counts, or ectoenzyme patterns. Double treatment with DMDP liposomes caused a marked leukocytosis in blood, primarily of lymphocytes and polymorphonuclear leukocytes (PMN), and a transient depression of spontaneous and interferon-inducible splenic NK activity. The effects on host resistance to i.v. infection with Listeria monocytogenes or herpes simplex virus type 2 (HSV-2) indicated that i.v. treatment with DMDP liposomes significantly reduced natural resistance to these microorganisms as evidenced by increased mortality and decreased median survival time. When DMDP liposomes-treated mice were given the immunomodulator maleic anhydride divinyl ether copolymer (MVE-2) intraperitoneally the day before infection with HSV-2, the immunosuppressive effect of DMDP liposome treatment was significantly reversed.
The Role of NK Cells in the Regulation of Experimental Metastasis in a Murine Lymphoma System
Authors: Smithson Glennda , Bittick Thomas H , Chervenak Robert , Lee Shu-Jan , Wolcott R Michael 
Published: January 2018

Abstract
This report describes the role of natural killer (NK) cells in regulating the localization of two closely related murine lymphomas (ASL1 and ASL1w) to various organ sites. These tumors are phenotypically similar yet differ in their overall malignancy and experimental metastatic pattern. Both tumors show similar patterns of migration in kinetic studies, however, they vary in their NK susceptibility. Cold target inhibition analysis and assessment of susceptibility to cytotoxic T lymphocytes (CTL) suggested that the NK resistance of ASL1 was due to the lack of expression of a relevant target structure(s) required for NK recognition. The role of NK cells in regulating the growth of the tumors in vivo was studied by altering NK cell levels in recipient mice prior to tumor injection. Neither NK cell depletion nor augmentation affected the growth of the NK resistant ASL1 tumor but NK depletion significantly shortened the mean survival time (MST) of recipients of the NK sensitive ASL1w tumor as well as changed its metastatic pattern; conversely, NK augmentation significantly increased the MST of ASL1w recipients. These data suggest that NK cells play a critical role in determining the metastatic characteristics of the ASL1w lymphoma.
Development, Differentiation, and Maturation of Macrophages in the Chorionic Villi of Mouse Placenta With Special Reference to the Origin of Hofbauer Cells
Authors: Takahashi Kiyoshi , Naito Makoto , Katabuchi Hidetake , Higashi Kenji 
Published: January 2018

Abstract
In blood vessels of the chorionic villi of mouse placenta, primitive macrophages first emerged at 10 days of gestation, then differentiated and matured into fetal macrophages. After emigration into the chorionic villous mesenchymal stroma, they ingested fluid-like stromal materials and transformed into Hofbauer cells. In our observation of their differentiation and maturation, no promonocytes or monocytes were detected. In the culture of cell suspensions from the placenta with LP3-conditioned medium, CFU-GM was confirmed, but in the culture with the mouse bone marrow stromal cell line (ST2) the primitive/fetal macrophage population occurred predominantly before the development of the monocyte/macrophage population. Proliferative potential of the primitive and fetal macrophages is slight. With the progress of gestation, the monocyte/macrophage population appeared in the chorionic villous stroma, forming a heterogeneous population of placental macrophages in the late fetal stage.
Effects of Corticosterone and Microgravity on Inflammatory Cell Production of Superoxide
Authors: Fleming Sherry D , Edelman Linda S , Chapes Stephen K 
Published: January 2018

Abstract
In this investigation we studied the effects of corticosterone and microgravity on Propionibacterium acnes-induced inflammatory cells ability to produce superoxide (O2-). We found in vitro and in vivo exposure of murine peritoneal inflammatory cells to corticosterone did not inhibit the O2- response. We also found that in microgravity P. acnes-induced inflammatory cells were capable of producing four times as much O2- as at 1g. Therefore, neither corticosterone nor microgravity experienced during parabolic flight prevents an O2- response by inflammatory cells.
Granulated Metrial Gland Cells: Pregnancy Specific Leukocytes?
Authors: Stewart I J 
Published: January 2018

Abstract
Granulated metrial gland (GMG) cells and their analogous cells are a prominent feature of the maternal placenta in rodents and in primates, including the human. Evidence which relates to the origin of these cells is reviewed and shows that there is now conclusive evidence that GMG cells are a type of leukocyte. Studies to define the type of leukocyte have been inconclusive overall, although several studies have suggested that GMG cells are a type of NK cell. However, it is proposed that attempting to define GMG cells as a type of leukocyte which is already known, like NK cells, is inappropriate and GMG cells should be considered as a separate leukocyte population. Granulated metrial gland cells are closely associated with pregnancy but technically cannot be described as pregnancy specific. The function of GMG cells remains to be established, but the possibility that GMG cells and their analogous cells are controlling the invasion of trophoblast into the uterine wall and/or the removal of aberrant trophoblast is currently under consideration.
Lipopolysaccharide-Dependent and Lipopolysaccharide-Independent Pathways of Monocyte Desensitisation to Lipopolysaccharides
Authors: Annenkov Alexander Y , Baranova Flora S 
Published: January 2018

Abstract
The present study demonstrates that with time in culture blood monocytes (MO) lose their ability to express procoagulant activity (PCA) and secrete tumor necrosis factor-alpha (TNFα) in culture medium in response to lipopolysaccharide (LPS) stimulation. Thus, upon 10 μg/ml LPS stimulation for 4 hours 2-day-old MO produced lower levels of PCA and TNFα than fresh MO. The decrease in responsiveness was not caused by cell death, since in the case of TNFα it was fully reversible by interferon-gamma (IFN-γ). Compared with cells pre-incubated in medium alone, the responsiveness of MO pre-incubated in LPS was further decreased. Thus, in MO LPS pre-incubation was followed by an LPS refractory state. It was expected that the decrease in responsiveness induced by cultivation in medium alone was mediated by LPS contamination of culture medium. However, as we were unable to prevent this decrease by neutralizing LPS contamination of the culture medium with polymyxin B, the loss in LPS-induced activities of cultured MO is likely to be mediated by culture conditions other than LPS contamination. Taken together the present data demonstrate that LPS-dependent as well as LPS-independent pathways of MO desensitization to LPS exist.
Viscoelastic and Motile Properties of Hamster Lung and Peritoneal Macrophages
Authors: Bizal Colette L , Butler James P , Valberg Peter A 
Published: January 2018

Abstract
The motile and rheologic properties of hamster lung and peritoneal macrophages (LMs and PMs) were examined by following the motions of magnetizable iron oxide (γ-Fe2O3) particles contained within phagolysosomes of these cells. As a measure of intracellular motility, γ-Fe2O3 particles in cells were magnetically aligned and the decay rate of the remanent magnetic field (RMF) in the direction of initial magnetization was monitored over time. Cytoplasmic rheology was measured by twisting the intracellular particles with a magnetic field (Btw) applied perpendicularly to the direction of initial magnetization. We measured changes in the RMF associated with application and removal of Btw. Intracellular motility in LMs and PMs was not significantly different (P &gt; 0.20); similarly, cytoplasmic viscosity was not significantly different in LMs and PMs (P &gt; 0.12); deformation on application of torque was significantly greater (P &lt; 0.0001) and elastic recoil on removal of torque was significantly smaller (P &lt; 0.0001) in PMs than in LMs; and by qualitative observation, the yield stress of cytoplasm (associated with a plastic, nonrecoverable deformation) was lower in PMs than in LMs. These results show that although cytoplasmic motion and viscosity are similar in the two cell types, PM cytoplasm is less stiff than LM cytoplasm as determined by yield stress.