bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of IL-1α, IL-1β, and 25K Mr Non-IL-1 Activity Released by Human Mononuclear Cells
Authors: Sandborg Christy I , Berman Monique A , Imfeld Karen L , Zaldivar Frank , Masada Marvin P , Kenney John S 
Published: January 2018

Abstract
To determine if the release of IL-1α and IL-1β by cultured PBMC could be independently modulated by different exogenous stimuli, we examined the effect of LPS, IFNγ, latex beads, and indomethacin on the release of IL-1α and IL-1β. PBMC culture supernatants were fractionated by Sephacryl-S-200 column chromatography or HPLC (TSK G3000SW), and each fraction was tested for thymocyte mitogenic activity in the presence or absence of preincubation with anti-IL-1α or anti IL-1β monoclonal antibody (mAb) and for the presence of IL-1α or IL-1β protein by ELISA. In all experiments, thymocyte mitogenic activity not neutralizable by anti-IL-1α or anti-IL-1β mAb was detected in the 25K Mr range, which ranged from 12 to 50% of the total thymocyte mitogenic activity released, depending on the stimuli. Cultured PBMC from 95% of individuals release thymocyte mitogenic activity in the absence of exogenous stimuli, which was increased 1.3- to 7-fold by lipopolysaccharide (LPS) (25–50 üg/ml). All of this increased activity was due to increased release of IL-1β and non-IL-1 thymocyte mitogenic activity, with no change in the total amount of IL-1α released. Indomethacin (0.1 μg/ml) induced release of increased thymocyte mitogenic activity of 1.3- to 1.4-fold over unstimulated cultures. All of this increased activity was due to increased release of IL-1α and non-IL-1 activity with a concomitant decrease in IL-1β release. Interferonγ (40–100 U/ml) increased the amount of IL-1α and decreased IL-1β and non-IL-1 activity released, resulting in no overall change in the total amount of thymocyte mitogenic activity.
Molecular weight fractionation of the PBMC culture supernatants revealed that thymocyte mitogenic activity eluting in the 25K Mr range was not due to IL-1α or IL-1β. With certain culture conditions, thymocyte mitogenic activity was detected in the 30–40K Mr range. PBMC cultured with LPS and latex beads in the absence of serum released 30–40K Mr IL-1α, as well as 17K Mr IL-1α and 17K Mr IL-1β. PBMC cultured in 2% fetal calf serum (FCS) alone from some donors released only 30–40K Mr thymocyte mitogenic activity. Both IL-1α and IL-1β protein was detected by ELISA in this Mr range but only the IL-1α was bioactive. This study shows that release of IL-1α, IL-1β, and non-IL-1 thymocyte mitogenic activity can be modulated by different stimuli in consistent patterns, and suggests that the release of these factors is independently regulated.
Differential Expression of Estrogen-Regulated CD4 and Ia Positive Cells in the Immature Rat Uterus
Authors: Zheng Yi , Sundstrom Susan A , Lyttle C Richard , Teuscher Cory 
Published: January 2018

Abstract
Estradiol treatment of sexually immature Sprague-Dawley, Cr:NIH-nu/+ and Cr:NIH-nu/ nu rats for 2 days results in a significant increase in the number of uterine eosinophils and OX-42 positive macrophages. However, only Sprague-Dawley rats exhibit an estrogen regulated increase in the number of cells expressing immunoreactive CD4 and la, suggesting that the differential responsiveness to the effects of estradiol between the two strains of rats may be genetically controlled. Nevertheless, Cr:NIH-nu/nu rats, which are deficient in T-cells, possess virtually identical numbers of CD4 positive staining uterine cells as compared to their nu/+ littermate controls, indicating that the expression of immunoreactive CD4 is associated with a resident non-T-cell population. In addition, a message for rat CD4 was observed in Northern blots of uterine mRNA, suggesting that the immunoreactive CD4 expressed by uterine cells is probably a fully functional cell surface antigen/receptor rather than a truncated form which only expresses the antigenic determinant recognized by the W3/25 monoclonal antibody.
Alterations of Host Resistance to Mouse Typhoid Infection by Sex Hormones
Authors: Kita Eiji , Yagyu Yoshihiko , Nishikawa Fumiko , Hamuro Akiko , Oku Daisuke , Emoto Masashi , Katsui Noriaki , Kashiba Shuzo 
Published: January 2018

Abstract
The effect on mouse typhoid infection of a 3-day treatment of female virgin mice with 1 mg/day of female sex hormones (estrogen or progesterone), maintaining the same hormonal levels observed in pregnant mice for 30 days, was investigated in order to clarify the mechanisms of altered resistance during pregnancy. Estrogen-exposed mice were more susceptible to the intraperitoneal challenge with Salmonella typhimurium as compared with the vehicle control mice, while progesterone treatment increased the survival times of mice. Estrogen exposure increased the number of peritoneal cells after treatment, but the inflammatory cellular response after infection was significantly suppressed. Although the estrogen-treated and vehicle control mice had the same degrees of peritoneal cellular responses after infection, the death rates in the estrogen-treated mice were higher than those in the vehicle control mice against challenge with 1 LD50 of S. typhimurium. On the other hand, progesterone treatment resulted in the marked influx of peritoneal cells after treatment was terminated, and also it induced a significant increase in the number of peritoneal cells after infection. Although survival times in the progesterone group were higher than those in other groups, all progesterone-treated mice died after a challenge with 1,000 LD50 of S. typhimurium. These results suggest that progesterone enhances nonspecific resistance by increasing the influx of peritoneal cells after infection, while estrogen affects the acute inflammatory responses.
Cooperation Between Platelets and Neutrophils for Paf-Acether (Platelet-Activating Factor) Formation
Authors: Coëffier Eliane , Delautier Danièle , Le Couedic Jean-Pierre , Chignard Michel , Denizot Yves , Benveniste Jacques 
Published: January 2018

Abstract
Association of platelets and neutrophils is frequently observed within thrombi or inflammatory sites. Interactions between these two cell populations have been reported for the production of several mediators of inflammation such as hydrogen peroxides or leukotrienes. Another potential mediator of thrombosis and inflammation is paf-acether, which is synthesized by activated platelets and neutrophils. Since platelets form and release large amounts of the paf-acether precursor lyso paf-acether, platelet and neutrophil cooperation for paf-acether biosynthesis was investigated. Purified human neutrophils (4 x 106/ml) stimulated by opsonized zymosan (ZC, 1 mg/ml) formed 4.5 ± 2.5 ng/ml paf-acether. Human washed platelets (3 x 108/ml) stimulated with thrombin (1 lU/ml) formed 0.60 ± 0.43 ng/ml paf-acether. Platelets and neutrophils, incubated together and both stimulated by their specific agonist, formed more than twice as much paf-acether as did platelets and neutrophils separately (10.90 ± 4.25 ng/ml, n = 6, P &lt; .001). The formation of lyso paf-acether and the release of lysozyme and LDH were unchanged under the cooperation conditions. The formation of paf-acether almost doubled (10.24 ± 3.81 ng/ml paf-acether vs. 5.30 ± 2.23, P &lt; .05, n = 4) when ZC-stimulated neutrophils were incubated with supernatants from thrombin-stimulated platelets as well as with synthetic lyso paf-acether. Extracted and purified lyso paf-acether from thrombin-stimulated platelets led to an increase of biosynthesis of paf-acether by neutrophils (13.86 ± 2.26 ng/ml paf-acether vs. 5.76 ± 0.38, P &lt; .05, n = 3).
These results indicate that a cooperation between platelets and neutrophils exists for paf-acether formation. The phenomenon depends on a platelet-derived soluble factor, possibly lyso paf-acether. This cell-to-cell interaction is of interest since paf-acether is formed by and acting on platelets and neutrophils and represents a molecular basis for potent amplification of inflammatory reactions.
Stimulus-Specific Effects of Pentoxifylline on Neutrophil CR3 Expression, Degranulation, and Superoxide Production
Authors: Currie Mark S , Rao K Murali K , Padmanabhan Jaya , Jones Adrie , Crawford Jeffrey , Cohen Harvey J 
Published: January 2018

Abstract
The effects of pentoxifylline (Trental) on human neutrophil CR3 up-modulation, degranulation, and superoxide production were studied. We used the chemotactic peptide fMLP and the phorbol ester PMA as soluble stimuli, and β-glucan particles as a CR3-specific solid phase stimulus of neutrophil superoxide production. Since neutrophils have adenosine A2 receptors, we compared effects of pentoxifylline to effects of adenosine, and we also looked at the effect of cytochalasin B, which breaks up actin filaments. Pentoxifylline inhibited both CR3 up-modulation and degranulation of myeloperoxidase and lysozyme. Pentoxifylline is a more potent inhibitor of fMLP- compared to PMA-induced degranulation, and is especially potent against superoxide production. While pentoxifylline is less potent than adenosine in its inhibiton of fMLP-induced superoxide production, it is more potent in its inhibition of PMA- and β-glucan particle-stimulated superoxide production. Cytochalasin B, which enhances degranulation and fMLP-stimulated superoxide production, was found to inhibit β-glucan particle-stimulated superoxide production. These findings are consistent with the hypothesis that pentoxifylline can affect both the cytoskeletal architecture of unstimulated neutrophils and the activation and responses of neutrophils which involve actin polymerization and receptor-cytoskeletal interactions.
Physiologic Oxygen Tensions Limit Oxidant-Mediated Killing of Schistosome Eggs by Inflammatory Cells and Isolated Granulomas
Authors: Feldman Gerald M , Dannenberg Arthur M , Seed John L 
Published: January 2018

Abstract
Explanted hepatic granulomas, eosinophils obtained from the peritoneal cavity of schistosome-infected mice, schistosome egg granuloma macrophages, alveolar macrophages, and activated peritoneal macrophages obtained from Listeria-infected mice were miracidicidal when cultured at 21% oxygen. This activity was markedly attenuated at physiologic oxygen concentrations (1–15%). Catalase and superoxide dismutase blocked the miracidicidal activity of inflammatory cells but did not prevent granuloma-mediated egg killing. However, the biomimetic superoxide dismutase, copper (II) [diisopropyl salicylate]2, inhibited granuloma-mediated egg killing in a dose-dependent, apparently nontoxic manner. Thioglycollate-elicited macrophages did not kill schistosome egg miracidia even when cultured in 21% oxygen, unless pretreated with lipopolysaccharide. Isolated schistosome eggs initiated an oxidative burst in macrophages, as measured by superoxide anion production. This burst was suppressed at reduced oxygen concentrations. Thus schistosome egg miracidia can be killed nonspecifically by macrophages through the release of cytotoxic reactive oxygen intermediates triggered by the egg. This activity is not supported by the oxygen concentrations found in most tissues, with the possible exception of the lung. Schistosoma mansoni eggs, injected intraveneously and lodged in the pulmonary vasculature of mice, were killed rapidly, with a half life of 3.5 days. Eggs, injected into the mesenteric veins and lodged in the liver, remained fully viable for several weeks. The data suggest that the high oxygen tension of the lung allows for the increased production of reactive oxygen intermediates (ROI) by local inflammatory cells, which in turn increases their miracidicidal efficiency. Conversely, the relatively hypoxic environment of the liver decreases ROI production by local inflammatory cells and decreases their miracidicidal efficiency.
Immunogold Labeling of the Low-Affinity (55 kd) IL2 Receptor on the Surface of IL2 Receptor-Bearing Cultured Cells and Mitogen-Activated Peripheral Blood Lymphocytes
Authors: McGroarty Roy J , Mills Gordon B , de Harven Etienne 
Published: January 2018

Abstract
Foreign antigens or mitogens initiate activation of T lymphocytes through antigen-specific receptors. After antigen-receptor interaction, T cells release a lymphotrophic hormone, Interleukin 2 (IL2), and high-affinity IL2 receptors (IL2R) are progressively expressed on their surfaces. When evaluated under the scanning electron microscope after specific immunolabeling with colloidal gold markers, the density of expression of the 55 kd low-affinity IL2 receptor (Tac) increases in a time-dependent manner, reaching a maximum 72 hours after the onset of phytohemagglutinin (PHA) activation. In contrast, the number of cells expressing the 55 kd molecule reaches a maximum by 24 hours and remains constant through 72 hours. Immunogold labeling allows simultaneous determination of IL2 receptor density at the level of each individual cell and of the percentage of IL2 receptor-positive cells in any cell population under study. The rank order of receptor expression on the surface of established culture cell lines correlates with results reported from other laboratories with immunofluorescence and Scatchard analysis of binding of radiolabeled IL2. Although at high density of receptor expression Immunogold labeling with 40 nm gold markers detects significantly fewer sites than radiolabeling, the method appears very sensitive in identifying low levels of expression. This results from 1) the extremely low non-specific background of the immunogold labeling technique and 2) the analysis of single cells rather than cell populations. Our results indicate that 2 cell lines, reported as negative for the expression of the 55 kd IL2 receptor (YT2C2 and MLA144), express low numbers of this molecule as demonstrated by immunogold labeling.
FcγRII-Mediated Superoxide Production by Phagocytes Is Augmented by GM-CSF Without a Change in FCγRII Expression
Authors: Roberts Pamela J , Devereux Steven , Pilkington Glenn R , Linch David C 
Published: January 2018

Abstract
Freshly purified neutrophils and monocytes respond to multiple cross-linking of FCγRII with the lgG1 monoclonal antibody, CIKM5, with a rapid rise in Ca(2+)I, but not with a respiratory burst, although superoxide is generated by these cells when stimulated with the chemotactic peptide, FMLP, or phorbol ester (TPA). Incubation in vitro for 30–60 min at 37°C in medium + 0.1% FCS had no effect on the neutrophil superoxide response to CIKM5 but induced a weak monocyte response in 11/13 experiments. However, incubation with rhGM-CSF (10 ng/ml) under similar conditions induced a neutrophil respiratory burst in response to cross-linking FcγRII in 12/14 experiments and enhanced the monocyte response by 181%. GM-CSF also enhanced the response of neutrophils and monocytes to FMLP by 308% and 165%, respectively. The response to TPA was not significantly enhanced by GM-CSF. rhlFN-γ (100 u/ml) was ineffective as a priming agent for all agonists tested in short-term incubations but augmented the monocyte response to CIKM5 after 5 d exposure in vitro. Whilst GM-CSF induced neutrophil superoxide production in response to cross-linking FcγRII, there was no concomitant change in FcγRII expression either in in vitro studies of neutrophils from healthy individuals or in in vivo studies of patients receiving GM-CSF. Stimulation of unprimed neutrophils with CIKM5 induced a rapid transient increase in intracellular calcium levels to 181% of resting levels. However, incubation with GM-CSF did not further augment the calcium transients above the stimulated level. The mechanism by which GM-CSF induces an enhanced respiratory burst in response to cross-linking of FCγRII remains to be elucidated, but is not related to receptor expression or increases in receptor mediated calcium mobilization.
Modulation of an Adhesion-Related Surface Antigen on Equine Neutrophils by Bacterial Lipopolysaccharide and Antiinflammatory Drugs
Authors: Bochsler Philip N , Slauson David O , Neilsen Nancy R 
Published: January 2018

Abstract
The essential role of the CD11/CD18 family of leukocyte adhesion molecules (LeuCams) in neutrophil-substrate adhesion is well documented. We have found that a monoclonal antibody designated 60.3 (MoAb 60.3) that recognizes the common β-subunit (CD18) on human neutrophils (PMN) also recognizes a surface antigen on equine PMN. Antigen expression as assessed by immunofluorescence flow cytometry was enhanced by zymosan-activated serum (ZAS) or phorbol 12-myristate 13-acetate (PMA) stimulation. Pretreatment of equine PMN with MoAb 60.3 inhibited ZAS-stimulated aggregation, indicating that the monoclonal recognized a functional epitope on equine PMN involved in adhesion-related functions. Cells pretreated only with bacterial lipopolysaccharide (LPS; 1 μg/ml) exhibited moderate increased binding of MoAb 60.3 as determined by fluorescence intensity. Preincubation of PMN with LPS resulted in a slight increase in MoAb 60.3 binding after subsequent ZAS stimulation, greater than that with either LPS or ZAS as sole stimulus. Similarly, enhanced binding of MoAb 60.3 was observed with LPS preincubation when PMA was used as a stimulus, but this effect was dose dependent and was observed at only one of three PMA concentrations tested (1 ng/ml). In other experiments, preincubation of PMN with antiinflammatory drugs inhibited 41.5–45.1% of ZAS-stimulated PMN adhesion to monolayers of equine endothelial cells. To determine whether modulation of expression of the adhesion-related antigen recognized by MoAb 60.3 correlated with these observed adhesive responses of PMN, we used immunofluorescence flow cytometry to assess expression of the antigen on drug-treated PMN. Using 10% ZAS as a stimulus, phenylbutazone (PBZ; 100 μg/ml) pretreatment of PMN reduced subsequent MoAb 60.3 binding by only 12.3%, and dexamethasone (DEX; 10-5 M) reduced binding by only 1.0%; reductions of 16.4% with PBZ and 9.3% with DEX occurred when PMA (10 ng/ml) was used as the PMN stimulant. These data suggest that equine PMN express a functional adhesion molecule similar to those found on human PMN and that LPS may enhance the expression of this surface antigen. Expression of this adhesion-related surface antigen on equine PMN does not correlate well with levels of drug-induced diminished adhesion of PMN to endothelium in vitro.
Failure of F-Met-Leu-Phe to Induce Chemotaxis in Differentiated Promyelocytic (HL-60) Leukemia Cells
Authors: Sirak Andrea A , Laskin Jeffrey D , Robertson Fredika M , Laskin Debra L 
Published: January 2018

Abstract
Treatment of HL-60 promyelocytic leukemia cells with dibutyryl cyclic adenosine 3′,5′-monophosphate (dbcAMP) induced these cells to differentiate toward mature neutrophilic granulocytes (PMN). DbcAMP was found to produce a rapid time- and dose-dependent inhibition of HL-60 cell proliferation, reaching a maximum after 48 hr treatment of the cells with 250–500 μM. This was associated with morphologic alterations consistent with maturing PMN. Using immunofluorescence and flow cytometry, we found that dbcAMP-treated HL-60 cells expressed some, but not all, surface markers characteristic of mature phagocytes. Thus receptors for the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP); the monocyte/granulocyte markers My-8, Mo-1, and Leu-15; as well as the monocyte markers Mo-2 and My-4 were identified on the cells. In contrast, dbcAMP-treated cells did not express the PMN-specific antigen DL1.2. We also found that dbcAMP-treated HL-60 cells produced hydrogen peroxide in response to the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA). However, the magnitude of this response was significantly less than that observed in mature PMN. In contrast, fMLP-stimulated levels of hydrogen peroxide production were comparable in both cell types. In addition, despite the fact that dbcAMP-treated cells expressed fMLP receptors, they did not exhibit directed migration toward this chemotactic peptide. Taken together, these data suggest that dbcAMP-induced differentiation of HL-60 cells is incomplete.
Fc-γ Receptor-Ligand Interactions Enhance Macrophage GSIB4-Binding Activity
Authors: Tabor Dale R , Thompson Joseph W , Lary Cynthia H , Jacobs Richard F 
Published: January 2018

Abstract
Activated macrophages have an increased ability to bind the lectin Griffonia simplicifolia-IB4 (GSIB4). Since macrophages readily use the Fc-receptor (FcR) during several immunologic and inflammatory processes, it is important to determine whether interactions with this moiety affect GSIB4-binding ability. Peritoneal macrophages cultured in vitro with Fc fragments of immunoglobulin G (IgG), whole IgG, or heat-aggregated IgG demonstrate an increase in this function. Conversely, treatment of macrophages with (Fab')2fractions alone has no direct effect on this activity. Although the GSIB4-binding response is minimally expressed by normal macrophages, it is more markedly apparent on macrophages from LPS-treated animals. In both cases, however, pretrypsinization of the cells renders them refractory to IgG-mediated induction of the GSIB4-binding response. Moreover, macrophages cultured independently with IgG subclasses 1, 2a, or 3 demonstrate that the magnitude of their response to this signal is directly associated with the type of subclass used. Although each subclass enhanced the response, in this study interactions with IgG2a produced the best results.
Overall, however, the greatest GSIB4-binding activity is generated when FcRs are crosslinked by aggregated IgG rather than simply bound by independent monomeric interactions at the FcRs. This suggests that the event of appropriately interacting with the FcRs amplifies the GSIB4-binding function. Such a mechanism could play a key role in coordinating the humoral, cell-mediated, and innate responses of the immune system.
Splenic Macrophages From Tumor-Bearing Mice Co-Expressing MAC-1 and MAC-2 Antigens Exert Immunoregulatory Functions Via Two Distinct Mechanisms
Authors: Watson Gordon A , Fu Yang-Xin , Lopez Diana M 
Published: January 2018

Abstract
Tumor burden has been shown to induce a variety of phenotypic and functional changes in the cellular constituents of the host's immune system. These changes have been implicated as mechanisms by which tumors avoid rejection. Studies of BALB/c mice bearing a D1-DMBA-3 mammary adenocarcinoma showed alterations of the splenocyte populations. There was a five-fold increase of macrophages (Mφ) that were phenotypically and functionally analyzed to establish their role in tumor-induced modifications of the host's immune response. Monoclonal antibody staining defined a Mac-1+2+ population which comprised up to 20% of the splenocytes in tumor-bearers (TB), but is negligible in spleens from normal mice. These Mao-1+2+ Mφ were found to mediate down-regulation of both polyclonal and antigen-specific T and B cell responses in vitro and in vivo. Although B cell responses were suppressed via prostaglandin E2 (PGE2) production by the TB Mφ, T cell responses were relatively refractory to PGE2-mediated down-regulation. Instead, they were suppressed by a contact-dependent T cell-Mφ interaction. Furthermore, tumor-derived factors such as granulocyte-Mφ colony-stimulating factor (GM-CSF) seem to play an important role in the induction and expansion of the Mac-1+2+ Mφ. These cells appear to mediate down-regulation of the host immune responses by at least two distinct mechanisms: 1) PGE2 production and 2) a cell contact-dependent, but non-major-histocompatibility-complex-specific, interaction.