bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transendothelial migration induces rapid expression on neutrophils of granule-release VLA6 used for tissue infiltration
Authors: Roussel Eugène , Gingras Marie-Claude 
Published: January 2018

Abstract
Little is known of the mechanisms allowing neutrophils to infiltrate tissue after transendothelial migration. We postulated that VLA6 might be involved in neutrophil infiltration because it revealed as the most expressed β1 integrins among VLA5, VLA4, and VLA3, which also appeared to define subsets within the blood neutrophil population. Transendothelial migration up-regulated by threefold (5,000 to 15,000 receptors) VLA6 expression on neutrophils. VLA6 up-regulation was transient, peaking in 6 min and returning to baseline in 1 h when tested in response to N-formyl-methionyl-leucyl-phenylalanine. Neutrophil degranulation experiments revealed a steady correlation between expression of VLA6 and granule content release, notably β-glucuronidase, indicating that VLA6 molecules were preformed and stored mostly in azurophilic granules. Migration across fibroblast monolayers of neutrophils preactivated for VLA6 up-regulation was blocked when they were preincubated with anti-VLA6. However, anti-VLA6 had no effect on transfibroblast migration of non-preactivated neutrophils. These results indicate that VLA6 was functional only on activated neutrophils that used their up-regulated VLA6 to cross fibroblasts. Activation of neutrophils by transendothelial migration induces rapid expression of granule release VLA6 that appears to be a key adhesion mechanism used by a subset of neutrophils to infiltrate tissue.
Rat monocytes up-regulate NKR-P1A and down-modulate CD4 and CD43 during activation in vivo: monocyte subpopulations in normal and IFN-γ-treated rats
Authors: Scriba Andreas , Schneider Michael , Grau Veronika , van der Meide Peter H , Steiniger Birte 
Published: January 2018

Abstract
LEW rats were treated intravenously with recombinant rat interferon-γ (IFN-γ) for 3 days to achieve intravascular accumulation, proliferation, and activation of monocytes. Monocytes, defined by their expression of the ED1, ED9, and Ox41 antigens, were recovered from the vasculature by perfusion with PBS/EDTA, subsequently depleted of erythrocytes and granulocytes by Percoll density gradient centrifugation, and analyzed by flow cytometry and immunocytology. In untreated and control-infused specified pathogen-free (SPF) rats, lymphocytes and monocytes formed overlapping cell populations with respect to size and internal granularity. At least two intravascular monocyte subsets, probably central and marginating cells, were distinguished by their size and differential expression of CD43, CD4, CD11a, CD18, and L-selectin. It is interesting to note that a fraction of the monocytes in normal and control-infused animals carried the NKR-P1A molecule. IFN-γ treatment provoked a duplication of monocyte size and granularity. Both the number of positive monocytes and the level of expression of NKR-P1A strongly increased after IFN-γ infusion, whereas CD43 (leukosialin) and CD4 were impressively down-regulated. NKR-P1A+ L-selectin+CD43low CD4- monocytes also occur in the vasculature of rats during immune reactions in vivo. We speculate that these cells are involved in organ damage and that their number is controlled by activation-induced cell death within the vessels.
Maintenance and down-regulation of primed neutrophil chemiluminescence activity in human whole blood
Authors: Brown Glenn E , Reiff Joel , Allen Robert C , Silver Geoffrey M , Fink Mitchell R 
Published: January 2018

Abstract
Priming of polymorphonuclear neutrophils (PMN) in whole blood (by tumor necrosis factor α and interleukin-8 for enhancement of luminoldependent chemiluminescence induced by human complement-opsonized zymosan) was stable for 120 min. In contrast, priming of isolated PMN in plasma-free suspension for responses to opsonized zymosan, formyl-methionyl-leucyl-phenylalanine, and phorbol myristate acetate was markedly less stable. Decay of priming was not due to irreversible inactivation of the terminal CL production machinery because PMN could be reprimed by platelet-activating factor or leukotriene B4. The tumor necrosis factor-α-primed state of isolated PMN was stabilized by host plasma in a concentration-dependent fashion. We conclude that PMN priming results in a dynamic state that is reversible. Our findings suggest the existence of blood-borne components that may act to stabilize or modify PMN priming.
PGG-Glucan activates NF-κB-like and NF-IL-6-like transcription factor complexes in a murine monocytic cell line
Authors: Adams David S , Pero Stephanie C , Petro J Benjamin , Nathans Robin , Mackin William M , Wakshull Eric 
Published: January 2018

Abstract
PGG-Glucan (Betafectin®) is a novel soluble β-glucan immunomodulator that enhances leukocyte microbicidal activities without inducing inflammatory cytokines. Although several different receptors for soluble and particulate β-glucans have been described, the signal transduction pathway(s) used by soluble β-glucans have not been elucidated. We report that in a murine monocytic cell line (BMC2.3) PGG-Glucan activates nuclear factor-κB (NF-κB)-like and NF-interleukin-6 (IL-6)-like transcription factors. Electrophoretic mobility shift assays showed that PGG-Glucan activation of the factors is time- and concentration-dependent. The NF-κB-like complex includes subunit p65 (rel-A) as one of its components, but apparently not p50 (κB1), p52 (κB2), p68 (rel-B), or p75 (C-rel) family members. The NF-IL-6-like complex contains subunit C/EBP-β (NF-IL-6α) as one of its components, but apparently not C/EBP-α or C/EBP-δ (NF-IL-6β). As expected, lipopolysaccharide (LPS) activated p65/p50 NF-κB and C/EBP-β NF-IL-6 complexes, increased the nuclear titer of p65 and p50 antigens, and increased cytokine (IL-1β, tumor necrosis factor α) mRNA production. In contrast, PGG-Glucan increased the nuclear titer of p65, but apparently not p50, and did not induce cytokine mRNA production, These data demonstrate that PGG-Glucan utilizes signal transduction pathways different from those used by LPS. The data suggest that activation of the PGG-Glucan-stimulated factors is not sufficient to stimulate cytokine mRNA transcription.
Induction of endotoxin tolerance depletes nuclear factor-κB and suppresses its activation in rat alveolar macrophages
Authors: Blackwell Timothy S , Blackwell Thomas R , Christman John W 
Published: January 2018

Abstract
To investigate the mechanism of endotoxin tolerance in macrophages, a rat alveolar macrophage cell line (NR8383) was rendered endotoxin tolerant by treatment with endotoxin at 40 ng/mL for 48 h. This treatment induced a state of tolerance such that subsequent exposure to high-dose endotoxin (5 μg/mL) resulted in decreased production of macrophage inflammatory protein-2, tumor necrosis factor α, and nitric oxide compared to endotoxin-sensitive cells. Suppressed mediator production by endotoxin-tolerant cells was associated with impaired activation of nuclear factor-κB (NF-κB) in response to treatment with 5 μg/mL of endotoxin. This impairment of NF-κB activation was found to be associated with depletion of latent NF-κB (both RelA and p50) in the cytoplasm of endotoxin-tolerant cells. These data suggest that a mechanism of endotoxin tolerance is depletion of RelA/ p50, which could limit the amount of NF-κB available for activation by subsequent stimuli and thereby inhibit transcription of NF-κB-dependent genes. Limiting NF-κB-dependent inflammatory gene transcription by inducing endotoxin tolerance is a potential therapeutic strategy for diseases where excessive production of inflammatory mediators leads to tissue injury.
Selectins and mechanisms of signal transduction
Authors: Crockett-Torabi Elahe 
Published: January 2018

Abstract
Leukocyte emigration is essential in both lymphocyte homing, as a central part of immune surveillance, and in leukocyte invasion at sites of inflammation. The emigration of leukocytes requires the interplay of adhesion molecules of the selectin and integrin families and chemokines. Selectindependent cell-cell interaction is essential in localizing leukocytes within tissues by promoting the rolling of leukocytes along the endothelial cell surface before development of tight adhesion and subsequent transendothelial migration. Selectins also play an active role in the initiation of intracellular signaling pathways and regulation of cell-cell interactions involving monocytes, lymphocytes, platelets, and endothelial cells. This review focuses mainly on the emerging evidence of biochemical signaling mechanisms involved in the regulation of selectin-dependent leukocyte activation and adhesion, as well as the critical role played by selectins as leukocyte stimulatory molecules. This evidence has serious implications regarding the development of immune and inflammatory responses. This article will also review key structural features of the selectin receptors. A summary is provided of our current understanding of the specific molecular interaction occurring between these adhesion molecules and their counter-receptors, focusing on the critical roles they may play in the regulation of functional responses.
Endogenous monocyte chemoattractant protein-1 recruits monocytes in the zymosan peritonitis model
Authors: Ajuebor Maureen N , Flower Roderick J , Hannon Robert , Christie Mark , Bowers Keith , Verity Anne , Perretti Mauro 
Published: January 2018

Abstract
The role of monocyte chemoattractant protein-1 (MCP-1) in the recruitment of blood-derived monocytes in a model of zymosan peritoneal inflammation was investigated. After zymosan injection (1 mg) a rapid influx of polymorphonuclear leukocytes (PMN) and monocytes into the peritoneal cavity associated with mouse MCP-1 (JE) gene activation and protein secretion in the exudates occurred. MCP-1 production (maximal at 4 h) preceded the accumulation of monocytes (F4/80-positive cells, maximally recovered between 16 and 24 h). Treatment of mice with a single injection of anti-mouse MCP-1 antibody inhibited 16-h monocyte accumulation by ~40%, however, a significant decrease in the number of PMN was also measured. Finally, intraperitoneal injection of murine recombinant MCP-1 (1 μg) produced a selective accumulation of monocytes (F4/80-positive cells) into the peritoneal cavity. In conclusion, we show the novel existence of a strict relationship between MCP-1 production and leukocyte accumulation in this model of acute inflammation.
Thermal injury-induced immunosuppression in mice: the role of macrophage-derived reactive nitrogen intermediates
Authors: Schwacha Martin G , Somers Scott D 
Published: January 2018

Abstract
Macrophages (MΦ) have been implicated in the suppression of lymphocyte function following thermal injury. Splenocytes isolated from C57BL/ 6NCR female mice 4–7 days after thermal injury displayed suppressed proliferative responses to Concanavalin A (ConA) and lipopolysaccharide (LPS) and high levels of reactive nitrogen intermediate (RNI) production. Inhibition of nitric oxide synthase activity with NG-monomethyl-L-arginine restored ConA responses but not LPS responses. Surprisingly, ConA-stimulated interferon-γ (IFN-γ) production was increased in splenocytes from injured mice. IFN-γ contributed to the RNI-mediated immunosuppression as antibodies against IFN-γ reduced RNI production and immunosuppression. ConA-stimulated co-cultures of splenic MΦ from injured mice and normal splenocytes produced high levels of RNI only under conditions of cellular contact and splenic mΦ from injured mice were capable of suppressing normal splenocytes responses in co-culture. These results indicate that MΦ activity and specifically RNI production contribute to the suppression of T lymphocyte function after thermal injury.
Protective effect of plasma in polymorphonuclear neutrophil-mediated cytotoxicity of endothelial cells in the systemic inflammatory response syndrome
Authors: Chen Xuwu , Christou Nicolas V 
Published: January 2018

Abstract
Polymorphonuclear neutrophil (PMN)-mediated endothelial cell (EC) cytotoxicity is well described in many in vitro systems. These observations have been extended in vivo and suggest that circulating PMNs adherent to endothelial cells can damage these endothelial cells and produce the capillary leak that is central to the evolution of a systemic inflammatory response to multiple organ failure. However, most PMC-EC interactions in the circulation must occur in the presence of plasma, therefore we studied PMN-induced endothelial cell cytotoxicity in the absence and presence of autologous plasma from healthy human volunteers and patients with the systemic inflammatory response syndrome (SIRS) requiring admission to an intensive care unit. PMNs from patients with SIRS had increased endothelial cell adherence compared with controls, but equivalent endothelial cell cytotoxicity. Endothelial cell activation with TNF-α and IL-1β markedly increased PMN adherence to endothelial cells. Plasma had a minimal effect on the adherence of PMNs to endothelial cells at baseline or after endothelial cell activation. In contrast, plasma provided endothelial cells with almost complete protection from PMN-induced cytotoxicity at baseline, as well as after endothelial cell activation in both human volunteers and patients with SIRS. The data suggest that PMNs may cause cytotoxic damage in end organs such as the lung only after they diapedese through the endothelial barrier into the extracellular matrix removed from the protective effect of circulating plasma.
Fas or ceramide induce apoptosis by Ras-regulated phosphoinositide-3-kinase activation
Authors: Gulbins Erich , Brenner Birgit , Koppenhoefer Ursula , Linderkamp Otwin , Lang Florian 
Published: January 2018

Abstract
We demonstrate a rapid and transient activation of phosphoinositide-3-kinase (PI-3-K) by Fas receptor triggering or cellular treatment with synthetic C6-ceramide. The stimulation of PI-3-K is critical for Fas or C6-ceramide-induced programmed cell death because transfection with a transdominant inhibitory PI-3-K construct or pretreatment with the PI-3-K inhibitor wortmannin almost completely prevented Fas or C6-ceramide-mediated apoptosis. Treatment with the caspase inhibitor Ac-YVAD-cmk or cellular transfection with transdominant inhibitory N17Ras prevented PI-3-K stimulation by Fas, suggesting that Fas activates PI-3-K via caspases and Ras. N17Ras expression also prevented C6-ceramide-initiated PI-3-K stimulation. The notion of a PI-3-K regulation by Ras upon Fas receptor ligation or ceramide treatment is supported by co-immunoprecipitation experiments revealing an activation-dependent association of PI-3-K and Ras.
Trypanosoma brucei infection elicits nitric oxide-dependent and nitric oxide-independent suppressive mechanisms
Authors: Beschin Alain , Brys Lea , Magez Stefan , Radwanska Magda , De Baetselier Patrick 
Published: January 2018

Abstract
During murine Trypanosoma brucei infection, macrophages contribute significantly to the inhibition of T cell responses. Although nitric oxide (NO) was shown to play a central role in macrophage-mediated splenic suppression, macrophage-mediated lymph node suppression occurred in an interferon-γ (IFN-γ)-dependent manner. In this study, using NO inhibitor NG-monomethyl-L-arginine and anti-IFN-γ antibodies, the relative contribution of NO and IFN-γ to the active inhibition of ex vivo concanavalin A-induced T cell proliferation taking place in the spleen and the lymph nodes of T. brucei-infected mice was investigated. NO contributes to the suppressive activity of spleen and lymph node cells only during early-stage infection. The existence of NO-independent suppressive pathway was further evidenced in IFN-γ-/--infected mice. Spleen cells from such animals do not produce NO but exert significant suppressive activity during the whole course of infection. In contrast in the lymph nodes, no suppressive activity is recorded at any moment of infection. Moreover, addition of exogenous IFN-γ to cultures containing lymph node cells from IFN-γ-/--infected mice does not impair proliferation despite NO production in such cultures. Thus during late-stage infection, an IFN-γ-independent suppressive mechanism is elicited in the spleen, whereas in the lymph nodes, IFN-γ is required yet not sufficient to inhibit T cell proliferation.
Chemokine synthesis in the HSV-1-infected cornea and its suppression by interleukin-10
Authors: Tumpey Terrence M , Cheng Hao , Yan Xiao-Tian , Oakes John E , Lausch Robert N 
Published: January 2018

Abstract
Herpes simplex virus type 1 (HSV-1) infection of the murine cornea results in a tissue-destructive inflammatory response. In this study we show that virus infection induces the synthesis of macrophage inflammatory protein-2 (MIP-2), MIP-1α, and monocyte chemoattractant protein-1 (MCP-1). However, only the production of MIP-2 and MIP-1α coincided with the influx of leukocytes into the cornea. IL-10 treatment markedly suppressed chemokine message and protein synthesis in vivo. Local administration of IL-10 also dramatically reduced the number of T cells and neutrophils migrating into the cornea and suppressed the severity of corneal disease. The inflammatory response could also be suppressed by the passive transfer of neutralizing antibody to MIP-1α but not MCP-1. We conclude that local IL-10 administration can suppress chemokine synthesis, thereby ameliorating corneal disease. Furthermore, our results indicate that MIP-1α plays a major role in herpes stromal keratitis development, whereas MCP-1 does not.
Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia
Authors: Delgado René , Carlin Andrea , Airaghi Lorena , Demitri Maria Teresa , Meda Lucia , Galimberti Daniela , Baron Pierluigi , Lipton James M , Catania Anna 
Published: January 2018

Abstract
Inflammatory processes contribute to neurodegenerative disease, stroke, encephalitis, and other central nervous system (CNS) disorders. Activated microglia are a source of cytokines and other inflammatory agents within the CNS and it is therefore important to control glial function in order to preserve neural cells. Melanocortin peptides are pro-opiomelanocortin-derived amino acid sequences that include α-melanocyte-stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH). These peptides have potent and broad anti-inflammatory effects. We tested effects of α-MSH (1-13), α-MSH (11-13), and ACTH (1-24) on production of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) in a cultured murine microglial cell line (N9) stimulated with lipopolysaccharide (LPS) plus interferon γ (IFN-γ). Melanocortin peptides inhibited production of these cytokines and NO in a concentration-related fashion, probably by increasing intracellular cAMP. When stimulated with LPS + IFN-γ, microglia increased release of α-MSH. Production of TNF-α, IL-6, and NO was greater in activated microglia after immunoneutralization of endogenous α-MSH. The results suggest that α-MSH is an autocrine factor in microglia. Because melanocortin peptides inhibit production of proinflammatory mediators by activated microglia they might be useful in treatment of inflammatory/degenerative brain disorders.
Adoptive immunotherapy of cancer using monocyte-derived macrophages: rationale, current status, and perspectives
Authors: Andreesen Reinhard , Hennemann Burkhard , Krause Stefan W 
Published: January 2018

Abstract
Adoptive transfer of host defense cells may be able to correct an otherwise defective generation of competent immune cells in patients with cancer. Ex vivo-grown cytotoxic macrophages (MAC) able to recognize and destroy tumor cells but not normal cells are effective in murine models of metastasizing tumors. After the development of large-scale technology to generate MAC in vitro from blood monocytes (MO), clinical trials in cancer patients have proven the feasibility and safety of infusing &gt;3 × 109 autologous MO-derived MAC activated by interferon-γ or lipopolysaccharide. Various modalities of adoptive immunotherapy with human MAC have been realized: routes of application used were intravenous, intraperitoneal, intrapleural, and through selective hepatic artery perfusion. In addition, MAC have been generated from MO collected after granulyte-macrophage colony-stimulating factor treatment in vivo. Biodistribution studies using 111indium-labeled cells have revealed localization of MAC to sites of bulk tumor growth on regional infusion as well as to liver metastases on systemic application. Malignant ascites disappeared in about 50% of patients after intraperitoneal treatment, yet no other evidence of therapeutic efficacy of MAC could be demonstrated. Further advances of adoptive transfer of MO-derived cells are developed with emphasis on the generation of antigen-presenting cells primed in vitro with tumor cells or specific peptides. J. Leukoc. Biol. 64: 419–426; 1998.
The identification and characterization of umbilical cord blood-derived human basophils
Authors: Kepley Christopher L , Pfeiffer Janet R , Schwartz Lawrence B , Wilson Bridget S , Oliver Janet M 
Published: January 2018

Abstract
Cross-linking allergen-specific immunoglobin E on human peripheral blood basophils results in the release of histamine and other inflammatory mediators that initiate allergy and asthma. The signaling pathways leading from IgE binding to mediator release have not been well established, mainly due to the difficulty in obtaining adequate numbers of highly purified basophils. It was the goal of this study to easily obtain FcεRI-positive human basophils in high yield and purity for studies of signal transduction pathways. We describe an in vitro culture system in which pulsing normal human cord blood leukocytes with interleukin-3 (IL-3) for 3–4 h followed by incubation in medium with fetal bovine serum generates a cell population that is predominately FcεRI positive between 14 and 28 days of culture. These cells resemble peripheral blood basophils when examined by light and electron microscopy. Like normal blood basophils, they express the integrins, CD11b, CD18, CD29, and CD49d. A majority of the IL-3-pulsed cells also express a marker recognized by the basophil-specific antibody, 2D7. FceRI cross-linking results in a time and dose-dependent release of histamine. FcεRI cross-linking also stimulates protein-tyrosine phosphorylation, thought to be the first event leading to the IgE-mediated activation of peripheral blood basophils. These studies establish cord blood as an accessible source from which basophil-like cells can be developed to examine FcεRI-mediated signal transduction. J. Leukoc. Biol. 64: 474–483; 1998.
Impact of aging on innate immunity
Authors: Pawelec Graham , Solana Rafael , Remarque Ed , Mariani Erminia 
Published: January 2018

Abstract
Immune responses in higher organisms are triggered by the recognition of a limited diversity of microbiological products by cells of the innate or “natural” immune system. As a result, in addition to the direct protective effect of natural immunity, antigen-presenting cells, particularly dendritic cells, are activated to process and present an enormous number of peptide antigens to the T lymphocytes of the adaptive immune system. These, together with the B lymphocytes, then mediate specific immune responses and maintain acquired immunological memory. The aging immune system is less well able to cope with infectious disease than the youthful immune system; this review will briefly consider what is known of the age-associated alterations in innate immunity, and how these may also impact on adaptive immunity. J. Leukoc. Biol. 64: 703–712; 1998.