bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation of specific antibodies against murine IL-1ra and the establishment of IL-1ra as an endogenous regulator of bacteria-induced fulminant hepatitis in mice
Authors: Fujioka Nakaba , Mukaida Naofumi , Harada Akihisa , Akiyama Mariko , Kasahara Tadashi , Kuno Kouji , Ooi Akishi , Mai Masayoshi , Matsushima Kouji 
Published: January 2018

Abstract
Blocking monoclonal antibodies (mAbs) specific to mouse interleukin-1 receptor antagonist (IL-1ra) were prepared by immunizing Armenian hamsters with recombinant mouse IL-1ra. A sensitive and specific ELISA against mouse IL-1ra was also established. In Propionibacterium αcnes-induced liver injury, P. acnes induced transient increase of serum tumor necrosis factor-α levels but not those of IL-1ra, IL-1, and IL-6. However, subsequent lipopolysaccharide (LPS) challenge induced the increase of serum levels of all these cytokines and the peak serum IL-1ra level was more than 20 times as high as serum IL-1 levels. Immunohistochemical analysis demonstrated that IL-1ra was predominantly produced by hepatocytes during the course of the priming phase by P. acnes and eliciting phase by LPS challenge. Furthermore, the administration of a mAb to mouse IL-1ra exacerbates the liver injury induced by P. acnes and sublethal dose of LPS, suggesting a protective role of endogenous IL-1ra in this liver injury model. J. Leukoc. Biol. 58: 90–98; 1995.
IL-10 up-regulates human monocyte phagocytosis in the presence of IL-4 and IFN-γ
Authors: Capsoni Franco , Minonzio Francesca , Ongari Anna Maria , Carbonelli Vincenzo , Galli Andrea , Zanussi Carlo 
Published: January 2018

Abstract
Interleukin-10 (IL-10), a cytokine produced by type 2 belper T (Th2) cells, inhibits the microbicidal effector function of interferon-γ (EFN-γ)-activated macrophages. However, recent observations indicate that IL-10, like IFN-γ, increases FcγRI expression and FcγR-mediated cytotoxic activity on human monocytes, suggesting that this cytokine cannot be classified purely as a monocyte deactivator. The present study found that incubation for 40 h of human monocytes or monocyte-derived macrophages in the presence of EL-10 caused a significant enhancement of their capacity to ingest particles coated with immunoglobulin G (FcγR-mediated ingestion) or with C3b/C3bi fragments of the complement system (GR1/CR3-mediated ingestion). The number of phagocytosing cells (% phagocytosis) and the number of ingested particles per cell (phagocytic index) were both significantly higher after 40-h incubation of monocytes with IL-10 concentrations ≥1 U/ml. This up-regulating activity on phagocytosis was completely reversed by anti-EL-10 monoclonal antibody (mAb). As previously reported, ILIO stimulated FcγRI expression on monocytes but did not induce the expression of FcγRII, FcγRIII, CR1, and CR3. IFN-γ, like EL-10, up-regulated only FcγRI expression but significantly reduced both FcγR- and CR-mediated ingestion. IL-10 almost completely reversed the IFN-γ-induced inhibition of both FcγR- and CR-mediated phagocytosis, without concomitant changes in membrane expression of phagocytic receptors. Exposure of monocytes to IL-4 reduced the membrane expression of all three FcγRs and also inhibited FcγR-mediated ingestion. On the other hand, IL-4 up-regulated both CR3 expression and CR-mediated ingestion on cultured monocytes. IL-10 not only neutralized the down-regulatory effect of IL-4 on FcγR expression but also completely reversed the IL-4-induced suppression of FcγR-mediated phagocytosis. Exposure of monocytes to a combination of IL-10 and IL-4 resulted in a synergistic effect on CR-mediated ingestion, even though no additive effects were observed on CR membrane expression. Finally, culture of monocytes in medium containing anti-EL-10 mAb significantly reduced their capacity to ingest IgG- or C3b/C3bi-coated particles, suggesting a role for endogenously produced IL-10 in the modulation of phagocytosis by human monocytes. These results demonstrate that IL-10 is a potent up-regulator of the phagocytic activity of human mononuclear phagocytes and indicate that this function may be in sensitive balance with the relative concentrations of EL-10, IL-4, and IFN-γ.
Function of the urokinase receptor (CD87) in neutrophil Chemotaxis
Authors: Gyetko Margaret R , Sitrin Robert G , Fuller Jennifer A , Todd Robert F , Petty Howard , Standiford Theodore J 
Published: January 2018

Abstract
During recruitment, leukocytes respond to chemotaxins and traverse matrix barriers. Urokinase-type plasminogen activator (uPA), bound to its receptor (uPAR; CD87) facilitates plasmin formation, which promotes matrix proteolysis. Polymorphonuclear leukocytes (PMNs) are critical to the inflammatory response and express both uPA and CD87. To determine whether uPA and CD87 are required for PMN Chemotaxis, PMNs were pretreated with an anti-CD87 monoclonal antibody (mAb), a neutralizing anti-uPA mAb, or uPA. PMN Chemotaxis was profoundly suppressed by the anti-CD87 mAb but was unaffected by anti-uPA mAb or uPA. The role CD87 plays in Chemotaxis may be related to its ability to associate with CR3. CD87/CR3 coupling can be disrupted by specific saccharides. The same saccharides that disrupt CD87/CR3 coupling (NADC, D-mannose, and mannoside) inhibit PMN Chemotaxis. We conclude that CD87 plays a crucial role in PMN Chemotaxis in vitro that is independent of uPA enzyme activity but may be related to the ability of CD87 to interact with CR3.
The role of tumor necrosis factor, interferon-γ, Transforming growth factor-β, and nitric oxide in the expression of immunosuppressive functions of splenic macrophages induced by Mycobacterium avium complex infection
Authors: Tomioka Haruaki , Sato Katsumasa , Maw Win Win , Saito Hajime 
Published: January 2018

Abstract
In order to verify the participation of some cytokines in the expression of the suppressor activity of splenic macrophages (Mφs) induced by Mycobacterium avium complex (MAC) infection, we studied whether anticytokine antibodies were capable of blocking their suppressor activity against concanavalin A (Con A)–induced mitogenesis of splenocytes (SPCs). When either anti-tumor necrosis factor (TNF), anti-Transforming growth factor-β (TGF-β), or anti-interferon-γ (IFN-γ) antibody was added to culture medium, suppressor activity was markedly reduced, in the order of anti-TNF, anti-IFN-γ, and anti-TGF-β antibodies. By contrast, neither anti-interleukin-6 (IL-6) nor anti-IL-10 antibody exerted such a blocking effect. Therefore, TNF, IFN-γ, and TGF-β seem to be related to the full display of the suppressor function of MAC-induced Mφs. However, TNF-α and IFN-γ but not TGF-β were substantially lacking in inhibitory action against SPC mitogenesis, when added exogenously. Hence, it is unlikely that TNF-α and IFN-γ directly modulated the proliferative response of T cells. On the other hand, both TNF-α and IFN-γ potentiated the effector function of the suppressor Mφs. Because their suppressor activity was severely reduced by NG-monomethyl-L-arginine and aminognanidine, nitric oxide (NO) synthase inhibitors, an NO-dependent mechanism is important for the expression of the immunosuppressive function of MAC-induced Mφs. Moreover, because these Mφs seem to produce a substantial amount of TNF-α in membrane-bound form, cell-to-cell contact might be needed for efficient expression of their suppressor action on target T cells.
A synthetic peptide containing a predominant protein kinase C site within p47phox inhibits the NADPH oxidase in intact neutrophils
Authors: Labadia Mark E , Zu You-Li , Huang Chi-Kuang 
Published: January 2018

Abstract
In vivo loading of a synthetic peptide (peptide 4) corresponding to residues 314–331 (RSRKRLSQDAYRRNSVRF) consistently diminished the oxidative burst in response to either phorbol 12-myristate 13-acetate (PMA) or formylmethionyl-leucyl-phenylalanine and cytochalasin B (fMLP/CB) compared to other synthetic peptides derived from the p47phox sequence. The effects of peptide 4 were concentration dependent with respect to both PMA and fMLP/CB. In contrast, peptide 4 enhanced the oxidative burst in response to fMLP alone. Peptide 4 inhibited the PMA and fMLP-mediated phosphorylation of endogenous neutrophil cytosolic proteins including p47phox. The PMA-induced translocation of p47phox to the plasma membrane was diminished in neutrophils loaded with peptide 4. These data represent the first report of a synthetic peptide derived from p47phox that inhibits the NADPH oxidase in intact neutrophils and inhibits the protein kinase C–mediated phosphorylation of endogenous p47phox.
Lipopolysaccharide regulates cysteine-rich intestinal protein, a zinc-finger protein, in immune cells and plasma
Authors: Hallquist Nora A , Khoo Christina , Cousins Robert J 
Published: January 2018

Abstract
Cysteine-rich intestinal protein (CRIP), a double zinc-finger LIM protein, is expressed in great abundance in the intestine. We have found comparable levels of CRIP mRNA in peritoneal macrophages, peripheral blood mononuclear cells (PBMC), and lesser amounts in thymus and spleen. Because CRIP expression was high in immune cells, rats were challenged with lipopolysaccharide (LPS) to determine whether expression was altered during the acute-phase immune response. Immunocytochemistry showed that, in adherent mononuclear cells, CRIP protein was localized in the cytoplasm. CRIP mRNA levels increased over time after LPS injection in peritoneal macrophages, PBMC, spleen, and intestine. No changes in CRIP mRNA level were seen in either liver or thymus. In PBMC, the level of CRIP mRNA decreased before increasing later in the acute-phase immune response. CRIP protein was found in the plasma. Shortly after LPS administration plasma CRIP decreased, suggesting that CRIP was either passively diffused out of capillaries or was actively shunted into tissues to execute its function. Increased CRIP expression seen in response to IPS suggests that CRIP may play a role in immune cell activation or differentiation or in processes associated with cellular repair.
Gadolinium induces macrophage apoptosis
Authors: Mizgerd Joseph P , Molina Ramon M , Stearns Rebecca C , Brain Joseph D , Warner Angeline E 
Published: January 2018

Abstract
Gadolinium (Gd) suppresses reticuloendothelial functions in vivo by unknown mechanisms. In vitro exposure of rat alveolar macrophages to GdCl3·6H2O caused cell death, as measured by trypan blue permeability, in both dose- and time-dependent fashions. Even a 10-min exposure to Gd caused significant cell death by 24 h. The morphology of Gd-treated cells, pyknosis and karyorrhexis prior to loss of membrane integrity, suggested apoptosis. Upon flow cytometric examination, Gd-treated propidium iodide-excluding cells demonstrated light scatter changes characteristic of apoptotic cells (decreased forward and increased right angle scatter). Gel electrophoresis of DNA from Gd-treated macrophages clearly showed the ladder pattern unique to apoptotic cells. Electron-dense structures containing Gd were observed via electron spectroscopic imaging within phagosomes and also within nuclei (associated with condensed chromatin). Gadolinium, endocytosed by macrophages and distributed to nuclei, causes apoptosis of macrophages in vitro.
In vitro characterization of rat bone marrow-derived dendritic cells and their precursors
Authors: Chen-Woan M , Delaney C P , Foumier V , Wakizaka Y , Murase N , Fung J , Starzl T E , Demetris A J 
Published: January 2018

Abstract
Although the rat is commonly used for basic immunology and transplantation research, phenotypic and functional characterization of rat dendritic cells (DCs) lags behind similar studies in the human and mouse. Therefore, these features were examined using DCs propagated from cultures of rat bone marrow maintained in a medium supplemented with granulocyte-monocyte colony-stimulating factor. Analysis of cytospin preparations of cultured cells showed that DCs arise from OX7+ myelomonocytic precursors. Typical mature rat DCs were morphologically similar to their mouse and human counterparts and expressed major histocompatibility complex (MHC) class II (common part determinant of Ia), OX62 (integrin molecule), OX7 (CD90), ICAM-1 (CD54), and CTLA4 counterreceptor, but were negative for OX8 (CD8), OX19 (CD5), W3/25 (CD4), and ED2, a rat macrophage marker. Functional analysis of OX62+ sorted DCs showed that they could effectively present the soluble antigen ovalbumin to naive T cells in vitro. A combination of anti-MHC class II monoclonal antibody and CTLA4-immunoglobulin inhibited allostimulatory ability more effectively than either reagent alone. Implications for studying the role of DCs in immune responses in the rat are discussed.
The role of CD11/CD18 integrins in the reverse passive Arthus reaction in rat dermal tissue
Authors: Rote William E , Dempsey Erin , Maki Steve , Vlasuk George P , Moyle Matthew 
Published: January 2018

Abstract
The GD11/CD18 leukocyte integrins are necessary for tissue localization of neutrophils, an early requisite event in inflammation. We have analyzed the contribution of CD11a/CD18 and CD11b/CD18 to local neutrophil accumulation and tissue injury in the reverse passive Arthus reaction in the rat dermis. Experimental groups comprised animals that an intravenous infusion of (1) recombinant neutrophil inhibitory factor (NIF), a hookworm-derived antagonist of CD11b/CD18; (2) monoclonal antibody to CD11a/CD18 (TA-3); (3) a combination of these agents; (4) a monoclonal antibody to CD18 (WT.3); or (5) saline. Administration of recombinant NIF or anti-CD11a/CD18 monoclonal antibody alone produced a slight reduction in neutrophil accumulation but did not affect edema formation. In contrast, a combination of these antagonists yielded a significant reduction in neutrophil accumulation and a modest reduction in edema, equivalent to levels observed with either anti-CD18 antibodies or animals that were rendered neutropenic. These results indicate that neutrophil infiltration in rat dermal tissue in the reverse passive Arthus reaction is dependent predominantly on the leukocyte integrins CD11a/CD18 and CD11b/CD18 and that either of these integrins is sufficient for neutrophil trafficking in this inflammatory setting.
Role of the type I interferons in allograft rejection
Authors: Tovey Michael G , Benizri Eric , Gugenheim Jean , Bemard Ghislaine , Eid Pierre , Blanchard Brigitte , Hofman Paul 
Published: January 2018

Abstract
Type I interferons are potent immuno-modulatory cytokines that enhance expression of the major histocompatibility complex (MHC) class I antigens, T-cell cytotoxicity, and natural killer (NK) cell activity, all of which are implicated in graft rejection. A monoclonal antibody (mAb) directed against the extracellular domain of the human interferon α (IFN-α) receptor (IFN-αR), which inhibits both the binding and biological activity of all the type I IFNs tested, exerted a dose-dependent inhibition of the mixed lymphocyte reaction and induced permanent survival of skin allografts in MHC-divergent Cynomologus monkeys treated with a subeffective dose of cyclosporin A. Marked differences were observed in the composition of T lymphocyte sub-populations in anti-IFN-αR mAb-treated animals relative to the various control groups. Skin biopsies from animals treated with anti-IFN-R Mab + cyclosporin A revealed very low levels of MHC class I and class II antigen expression and the absence of histological signs of rejection, whereas skin biopsies from control animals exhibited high levels of MHC antigen expression and the histological signs of acute rejection, including a pronounced lymphocytic infiltrate, edema, and necrosis. No monkey antibodies (IgG) to the mouse anti-human IFN-αR mAb were detected in the serum of any of the animals treated with the anti-IFN-αR mAb either alone or together with cyclosporin A. Treatment of lethally irradiated Cynomologus monkeys with the anti-IFN-αR mAb together with a subeffective dose of cyclosporin A was also found to markedly enhance the survival of animals grafted with allogeneic bone marrow cells from donors differing in both MHC class I and class II antigens. These results show that selective and lasting immunosuppression can be obtained by the short-term administration of an IFN-α antagonist together with a subeffective dose of cyclosporin A, and may have important implications for the therapy of human allograft rejection.
Transcriptional and post-transcriptional regulation of GM-CSF-induced IL-1β gene expression in PMN
Authors: Fernandez Marilyn C , Walters John , Marucha Phillip 
Published: January 2018

Abstract
Polymorphonuclear leukocytes (PMN) play an important role in inflammation, immune responses, and tissue repair by secreting interleukin-1β (IL-1β). We investigated the regulation of IL-1β gene expression in human PMN treated with granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF induced IL-1β mRNA accumulation at 0.1 ng/ml and maximal induction was observed at 1 ng/ml. IL-1β mRNA levels reached a maximum within 1–2 h after stimulation with GM-CSF and returned to baseline levels by 4–6 h. The time course of IL-1β mRNA induction by GM-CSF was more protracted than previously reported for PMN stimulated with tumor necrosis factor-α (TNF-α, 10 ng/ml). Nuclear run-on analysis indicated that GM-CSF, like TNF, increases IL-1β transcription. Kinetic studies with the RNA synthesis inhibitor, actinomycin D, showed that GM-CSF induces stable IL-1β mRNA. Cycloheximide enhanced the IL-1β mRNA accumulation by GM-CSF at the level of mRNA stabilization, but blocked IL-1β mRNA expression by TNF. Thus, GM-CSF increases IL-1β message accumulation in PMN at both the transcriptional and post-transcriptional levels by mechanisms that are different from TNF induction of IL-1β gene expression.
GM-CSF-induced in vivo expansion of splenic dendritic cells and their strong costimulation activity
Authors: Hanada Ken-ichi , Tsunoda Rikiya , Hamada Hirofumi 
Published: January 2018

Abstract
Dendritic cells (DC), with their potent antigen-presenting and accessory activities, are involved in the stimulation of naive T cells. To examine the biological functions of DC, we developed a method for generating large numbers of murine splenic DC. First, DC were propagated in vivo by using a granulocyte-macrophage colony-stimulating factor-secreting tumor as a continuous in vivo source of the cytokine. The DC enriched in the spleen, especially in the white pulps, were purified after an overnight culture. We could reproducibly obtain 6 to 10 106 splenic DC per mouse. These DC were morphologically similar to interdigitating cells, expressed high levels of MHC class II and costimulatory molecules, and were highly allo-stimulatory in mixed lymphocyte reactions. Further analysis on T cell stimulation activity revealed that the DC had strong costimulatory activity on human T cells. Activated B cells, which express both B7-1 and B7-2, had little T cell costimulatory activity under the same assay conditions. A human histiocytic leukemia cell line, U937, that showed only weak costimulatory activity by itself, worked synergistically with DC and further intensified the T cell stimulation by DC. These findings suggest the presence of a T cell costimulation mechanism in DC, which is activated synergistically by monocytes or macrophages, and deserves further study.
Control of nitric oxide production by endogenous TGF-β1 and systemic nitric oxide in retinal pigment epithelial cells and peritoneal macrophages
Authors: Vodovotz Yoram , Letterio John J , Geiser Andrew G , Chester Louis , Roberts Anita B , Sparrow Janet 
Published: January 2018

Abstract
Both in vivo and in vitro experiments demonstrate that transforming growth factor-β1 (TGF-β1) suppresses expression of the inducible form of nitric oxide synthase (iNOS). In this study, we examined the effects of exogenous and endogenous TGF-β1 on retinal pigment epithelial (RPE) cells and resident peritoneal macrophages ex vivo using cells from TGF-β1 null (TGF-β1-/-) mice or age-matched wild-type (TGF-β1+/+) or heterozygous (TGF-β1+/-) littermates. RPE cells from both TGF-β1-/- mice and TGF-β1+/+ littermates produced NO and were immunocytochemically positive for iNOS protein only following treatment with interferon-γ (IFN-γ) and bacterial lipopolysaccharide (LPS); however, RPE cells from TGF-β1-/- mice produced 40% more NO than cells from TGF-β1+/+ mice. In contrast, resident peritoneal macrophages from both TGF-β1+/+ and TGF-β1-/- mice expressed iNOS protein without stimulation and in the absence of detectable production of NO. The expression of iNOS was increased by treatment with IFN-γ, resulting in detectable levels of NO. Macrophages from TGF-β1+/+ mice appeared to produce NO in a manner inversely proportional to the serum content of NO2- and NO3- of the mice from which the cells were obtained; no such correlation existed in TGF-β1+/- or TGF-β1-/- mice. Treatment of RPE cells or macrophages from both TGF-β1+/+ and TGF-β1-/- mice with exogenous TGF-β1 decreased both iNOS protein and NO production. These findings demonstrate a novel role of endogenous TGF-β1 in coupling systemic NO production to the production of NO by macrophages, and demonstrate that endogenous and exogenous TGF-β1 can act differently to suppress NO production.
Interaction of murine dendritic cells with collagen up-regulates allostimulatory capacity, surface expression of heat stable antigen, and release of cytokines
Authors: Mahnke Karsten , Bhardwaj Ranjit S , Luger Thomas A , Schwarz Thomas , Grabbe Stephan 
Published: January 2018

Abstract
In vivo, dendritic cells (DC) reside in direct proximity to extracellular matrix (ECM) proteins. Because ECM proteins affect morphology and function of a number of cell types, this study investigated potential effects of ECM proteins on functional properties of DC. DC were generated from murine bone marrow cultures, supplemented with granulocyte-macrophage colony-stimulating factor, and subsequently cultured on tissue culture plates coated with various ECM proteins. Among the ECM proteins tested, collagen (COL) up-regulated the T cell stimulatory capacity of DC. This effect was accompanied by sustained surface expression of the co-stimulatory molecule heat stable antigen on DC and by enhanced release of interleukin-1 and interleukin-6, respectively. Because fibronectin or solubilized COL were unable to cause similar changes in DC phenotype or function, we conclude that adherence to COL interferes specifically with DC function. These data suggest that ECM proteins may be involved in regulation of DC phenotype as well as in their functional activation.
Regulation of microglial activation by TGF-β, IL-10, and CSF-1
Authors: Lodge Patricia A , Sriram Subramaniam 
Published: January 2018

Abstract
Microglia are the resident macrophages of the brain and as such are active participants in immune responses in the central nervous system. Normal resting microglia express low levels of MHC class I and class II antigens and do not produce proinflammatory cytokines. However, microglial immune functions are induced in areas of infection or injury. To understand regulation of cytokines that are secreted by and act upon microglia, we examined production of interleukin (IL) -12, tumor necrosis factor-α (TNF-α), and nitric oxide (NO) by lipopolysaccharide (LPS)-stimulated microglia. We observed secretion of IL-12, TNF-α, and NO following stimulation of microglia with LPS. Addition of IL-10 suppressed TNF-α, IL-12, and NO production. Transforming growth factor-β (TGF-β) also inhibited TNF-α and NO but did not affect IL-12 secretion. IL-12 secretion became sensitive to TGF-β inhibition when microglia were cultured in the absence of CSF-1. In addition to its effect on the response to TGF-β, CSF-1 suppressed the response of microglia to LPS. These data suggest that CSF-1 may contribute to the immunologic ally privileged status of the central nervous system.