bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maleylated-BSA induces hydrolysis of PIP2, fluxes of Ca2+, NF-κB binding, and transcription of the TNF-α gene in murine macrophages
Authors: Misra Uma K , Shackelford Rodney E , Florine-Casteel Kathryn , Thai Sheau-Fung , Alford Paul B , Pizzo Salvatore V , Adams Dolph O 
Published: January 2018

Abstract
The Interaction of altered lipids or proteins with the several scavenger receptors (SR) on macrophages can lead to disparate results in both gene expression and cell function. However, the molecular bases of signaling induced by SR ligation have remained obscure. Here we report that maleylated-bovine serum albumin (maleyl-BSA) binds a low-affinity SR, initiating POP2 hydrolysis, [Ca2+J spikes, phospholipase A2 (PLA2) activation, nuclear factor-κB (NF-κB) binding to its cognate nucleotide and tumor necrosis factor α (TNF-α) gene transcription. We recently reported that oxidized low-density lipoprotein (ox-LDL), which binds another macrophage SR, induced pertussis-toxin-sensitive hydrolysis of PIP2 and elevations in [Ca2+]i [J. Biol. Chem. 270, 3475–3478, 1995]. By contrast, maleyl-BSA-initiated events were not pertussis toxin-sensitive and produced less [Ca2+]i spiking than ox-LDL. Furthermore, maleyl-BSA led to binding of NF-κB to its cognate nucleotide and TNF-α gene transcription, whereas ox-LDL suppressed these events. Collectively, this data suggests that maleyl-BSA and ox-LDL bind to distinct SR on murine macrophages, initiate distinct signal transduction pathways, and produce different functional effects.
Monoclonal antibodies against the human mannose receptor as a specific marker in flow cytometry and immunohistochemistry for macrophages
Authors: Noorman Femke , Braat Ellen A M , Barrett-Bergshoeff Marrie , Barbé Ellis , van Leeuwen Alexander , Lindeman Jan , Rijken Dingeman C 
Published: January 2018

Abstract
Recently we developed mouse monoclonal antibodies (mAb) against the isolated human 175-kDa mannose receptor. In the present study we tested whether these mAb are suitable for the detection of the mannose receptor on cultured macrophages using flow cytometry and on cells in human tissues using immunohistochemistry. Human monocytes did not react with the mAb in flow cytometry. Mannose receptor expression became detectable on monocytes cultured for 3 days (macrophages), and was maximal from 4 days onward. The mannose receptor was up-regulated on dexamethasone-treated (immunosuppressed) macrophages, and down-regulated on lipopolysaccharidetreated (activated) macrophages. Immunohistochemically the staining pattern of our mAb was compared with the marker of monocytes/macrophages KP1. In a bone marrow smear, only macrophages were stained with our mAb, whereas all myeloid cells were stained with KP1. In the thymus and lymph node, mannose receptor-positive branched cells (macrophages and dendritic cells) were detected in connective tissue, thymus cortex (not medulla), and in the T cell area (not the B cell area) of lymph nodes, whereas KP1 stained branched cells in all areas. It was concluded that the mAb are useful tools in flow cytometry and immunohistochemistry for the specific detection of cells expressing mannose receptor.
Mig and IP-10: CXC chemokines that target lymphocytes
Authors: Farber Joshua M 
Published: January 2018

Abstract
Mig and IP-10 are related members of the CXC subfamily of the chemokine family of cytokines. The murine Mig (MuMig), human IP-10, and the mouse homologue of IP-10, Crg-2, were all identified due to the dramatic inductions of their genes in monocytic cells treated with interferon-γ (IFN-γ). Studies using recombinant (r) human proteins show that, unlike most other CXC chemokines, rHuMig and rIP-10 have no activity on neutrophils but appear to target lymphocytes specifically. rHuMig and rIP-10 are active as chemotactic factors for stimulated, but not for resting, T cells. Studies done in vitro and in vivo have shown that rHuMig and rIP-10 share additional activities, including inhibition of neovascularization, inhibition of hematopoietic progenitor cells, and anti-tumor effects. rHuMig and rIP-10 show reciprocal desensitization on activated T cells and have been demonstrated to share a receptor, CXCR3. The genes for both MuMig and Crg-2 are highly expressed in multiple tissues during experimental viral and protozoan infections in mice, but their patterns of expression differ. This suggests that the Migs and IP-10/Crg-2 may play roles in host defense and that, despite their similar activities assayed in vitro, Mig and IP-10/Crg-2 may serve non-redundant functions in vivo.
Expression of endothelial adhesion molecules and recruitment of neutrophils after traumatic brain injury in rats
Authors: Carlos T M , Clark R S B , Franicola-Higgins D , Schiding J K , Kochanek P M 
Published: January 2018

Abstract
Traumatic brain injury (TBI) is often accompanied by an acute inflammatory reaction mediated initially by neutrophils. Adhesion molecules expressed on vascular endothelium are requisite elements during recruitment of leukocytes at sites of inflammation. In a rat model of TBI the induction and persistent expression of E-selectin (CD62E) on cerebrovascular endothelium ipsilateral, but not contralateral, to the site of contusion was demonstrated (P &lt; 0.05 at 4 and 48 h posttrauma). In addition, these studies confirmed up-regulation and prolonged expression of ICAM-1 (CD54) on endothelium in the traumatized hemisphere (P &lt; 0.05 at 4, 24, 48, and 72 h posttrauma). It is of interest that increased expression of CD54 was noted on blood vessels in the contralateral, non-traumatized hemisphere 48 h posttrauma. Expression of a third endothelial adhesion molecule, PECAM-1 (CD31), was unchanged following trauma. Administration of a murine monoclonal antibody (TM-8) that inhibits the adhesive function of CD54 blocked a significant portion (37.9%) of neutrophil recruitment 24 h posttrauma (P = 0.04). Employing immunocytochemistry and a monoclonal antibody specific for rat neutrophils (RP-3), peak infiltration of neutrophils was shown to occur 48 h after trauma. In contrast to emigration of neutrophils from blood vessels within the contusion, however, entry of neutrophils occurred from the surrounding leptomeninges and choroidal vessels. These studies demonstrate the relevance of CD54 (ICAM-1) in recruitment of neutrophils following TBI. However, the majority of neutrophil influx relies on endothelial adhesion molecules other than CD54. Because emigration of neutrophils was shown to occur predominantly from vessels within the leptomeninges and choroid plexus, intrathecal delivery of agents that inhibit the adhesive interactions between neutrophils, endothelial CD54, and other endothelial adhesion molecules to be defined may offer a novel form of therapy to prevent the acute inflammatory response that follows TBI.
Establishment of an IL-12-responsive T cell clone: its characterization and utilization in the quantitation of IL-12 activity
Authors: Maruo Seiji , Ahn Hyun-Jong , Yu Wen-Gong , Tomura Michio , Wysocka Maria , Yamamoto Norihiko , Kobayashi Michiko , Hamaoka Toshiyuki , Trinchieri Giorgio , Fuijiwara Hiromi 
Published: January 2018

Abstract
We previously demonstrated that proliferation of terminally differentiated Thl clones depends primarily on an interleukin-12 (IL-12)-paracrme mechanism mediated by their interactions with antigen-presenting cells (APC) rather than on an IL-2-autocrine mechanism. Such a Thl clone (4-86, C57BL/6 origin) was cultured with recombinant IL-12 (rIL-12) in the absence of either antigen or APC. Some cells survived for several passages of culture with only rIL-12, and by limiting dilution, several clones highly reactive to rIL-12 alone were obtained. One of these clones, designated 2D6, was found to proliferate strongly in response to less than 1 pg/mL of rIL-12. This clone exhibited the following surface phenotypes: CD3+, T cell receptor (TCR) αβ+, Vβ11+, NK-1.1-; CD4- CD8-; LFA-1+, ICAM-1+; and CD28+, CD80+, CD86+, CTLA-4-. In accordance with high responsiveness to IL-12, 2D6 cells were also found to express IL-12 receptor (IL-12R) as detected by incubation with rIL-12 and then staining with anti-IL-12 monoclonal antibody (mAb). Stimulation of 2D6 with rIL-12 resulted in the expression of interferon-γ (IFN-γ) and IL-10 mRNAs and production of these cytokines. The 2D6 clone responded to IL-2 (vigorously), IL-7 (moderately), and IL-4 (mildly) in addition to IL-12. However, the Ab capture assay using anti-IL-12 mAb enabled us to quantify IL-12-specific activity contained in a given sample. Thus, this study describes the unique features of the IL-12-responsive T cell clone and demonstrates the utilization of this clone in the quantitation of a specific IL-12 activity.
Dendritic cell maturation is required for initiation of the immune response
Authors: Rescigno Maria , Winzler Claudia , Delia Domenico , Mutini Carmela , Lutz Manfred , Ricciardi-Castagnoli Paola 
Published: January 2018

Abstract
Dendritic cells (DC) are professional antigen-presenting cells (APC) whose primary function is to capture, process, and present antigens to unprimed T cells [1, 2]. They comprise a system of leukocytes widely distributed in all tissues, especially in those that provide an environmental interface (skin and mucosal surfaces) and in lymphoid organs [1].
LPS-induced blood neutrophilia is inhibited by α1-adrenoceptor antagonists: a role for catecholamines
Authors: Altenburg Sonia P , Martins Marco A , Silva Adriana R , Cordeiro Renato S B , Castro-Faria-Neto Hugo C 
Published: January 2018

Abstract
A role for catecholamines in the regulation of the blood neutrophilia induced by intravenous (i.v.) injection of lipopolysaccharide (LPS; 250 μg/kg) was examined in Wistar rats by means of surgical adrenalectomy or pretreatment with adrenergic and dopaminergic antagonists into naive animals. Treatment of animals with a single dose (250 μg/kg) of LPS caused a dramatic increase in the number of circulating neutrophils concomitant with a decrease in the number of these cells in the bone marrow. These effects were partially reversed when catecholamine stores were depleted with reserpine. It was found that neither adrenalectomy nor pretreatment with the dopaminergic antagonists, chlorpromazine and pimozide, affected the changes in neutrophil counts induced by LPS. The injection of the α1/α2-adrenoceptor antagonist, phentolamine, and the selective α1-adrenoceptor antagonist, prazosin, significantly decreased blood neutrophilia induced by LPS. However, neither the selective (α2-adrenoceptor antagonist, yohimbine, nor the β-adrenoceptor antagonist, propranolol, had any effect on LPS response. Taken together, these findings support the hypothesis that the catecholamine norepinephrine plays a role in the regulation of the LPS-induced neutrophilia through activation of α1-adrenoceptors. J.
Targeting antiviral nucleotide analogues to macrophages
Authors: Magnani Mauro , Rossi Luigia , Fraternale Alessandra , Casabianca Anna , Brandi Giorgio , Benatti Umberto , De Flora Antonio 
Published: January 2018

Abstract
Macrophages are important target cells for human immunodeficiency virus type 1 (HIV-1) infection. We have developed a drug targeting system for the selective delivery of phosphorylated nucleoside analogues to these phagocytosing cells. This system is based on the possibility of encapsulating the phosphorylated drugs into autologous erythrocytes and on the subsequent selective modification of their membranes to promote macrophage recognition and phagocytosis. Targeted delivery of phosphorylated nucleoside analogues to human, feline, and murine macrophages inhibits the infectivity of HIV-1, feline immunodeficiency virus, and LP-BM5 viruses more efficiently than the administration of the corresponding nucleoside analogues. In vivo administration of 2′,3′-dideoxycytidine 5′-triphosphate (ddCTP) encapsulated into autologous erythrocytes to LP-BM5-infected mice was found to reduce infectivity and disease progression. Furthermore, the simultaneous administration of AZT or ddC produced additive antiviral effects. The possibility of using red cells as drug targeting systems was useful for the design, synthesis, and delivery of new antiviral nucleoside analogues. As a prototype of these new drugs, di-(thymidine-3′-azido-2′,3′-dideoxy-D-riboside)-5′-5′-p1-p2-pyrophosphate (AZTp2AZT) was prepared. Although this drug in solution has the same antiviral activity as AZT, when administered encapsulated into erythrocytes it was several times more efficient in inhibiting the infectivity of human, feline, and murine immunodeficiency viruses. Thus, the availability of a drug targeting system for the selective delivery of antivirals to macrophages offers an additional possibility for the development of new drugs and of new combination antiviral therapies.
Natural killer cells: Endothelial interactions, migration, and target cell recognition
Authors: Timonen Tuomo 
Published: January 2018

Abstract
Natural killer (NK) cells form a unique third group of lymphocytes that differs from T and B cells in surface phenotype, target recognition, and function. By producing cytokines and exerting cytotoxicity, NK cells participate in the resistance against microbial infections and malignant disease. The research on the molecular mechanisms of migration and target cell recognition by NK cells has recently developed rapidly. NK cells express a number of adhesion molecules common to hematopoietic lineage, bind to endothelium, extravasate, and respond to chemotactic stimuli, much resembling T cells in those respects. However, NK cells are probably capable of transmigration and infiltration merely through activation by cytokines and chemokines, as opposed to the requirement of antigen presentation in the initial activation of T cells. Target cell recognition and ensuing cytotoxicity of NK cells is a sum effect of a delicate balance between the effects of inhibitory and activating NK cell receptors. NK cells express several well-defined MHC I-recognizing receptors that inactivate their functions. In pathological alterations of MHC I expression, the inhibitory receptors do not engage and thus permit the lysis of the target cell. The receptors that trigger the cytolytic machinery of NK cells are less well known. Some candidate triggering receptors have been identified and it seems that NK cell triggering is mediated by multiple receptors, as is the inhibition of cytotoxicity. For example, NK cells clearly detect target cell-bound antibodies and thus mediate antibody-dependent cytotoxicity. They may also detect carbohydrate moieties, normal but pathologically distributed adhesion molecules, as well as ligands for a number of co-stimulatory receptors.
Agonist-specific tyrosine phosphorylation of Cbl in human neutrophils
Authors: Naccache Paul H , Gilbert Caroline , Barabé Frédéric , Al-Shami Amin , Mahana Wahib , Bourgoin Sylvain G 
Published: January 2018

Abstract
The effects of soluble and particulate agonists on the tyrosine phosphorylation levels of the proto-oncogene Cbl in human neutrophils were examined. Experimental conditions allowing the maintenance of Cbl as well as of its tyrosine phosphorylation status were first established. Their use allowed us to observe that Cbl was tyrosine phosphorylated in response to some (FcγRII ligation, opsonized bacteria and zymosan, granulocyte-macrophage colony-stimulating factor, monosodium urate, and calcium pyrophosphate microcrystals), but not all (fMet-Leu-Phe, interleukin-8) neutrophil agonists. Cbl was also shown to account for a varying proportion of the 120-kDa phosphoprotein(s) observed in response to the above stimuli. These data establish that Cbl is present in human neutrophils and that its level of tyrosine phosphorylation is modulated by some of these cells' agonists, and in particular by phagocytic particles. Furthermore, the signaling pathways activated by chemotactic factors and the other neutrophil stimuli tested in this investigation diverge at or downstream from the tyrosine phosphorylation of Cbl.
Inhibition of LPS-mediated activation in rat Kupffer cells by N-acetylcysteine occurs subsequent to NF-κB translocation and requires protein synthesis
Authors: Fox Eben S , Leingang Karen A 
Published: January 2018

Abstract
Activation of the resident hepatic macrophage population, Kupffer cells, leads to production of mediators that initiate, potentiate, and modulate hepatic injury. Recent studies have shown that activation of the pluripotent transcription factor nuclear factor-κB (NF-κB) is an important step in the induction of inflammatory cytokines, chemokines, growth factors, cell adhesion proteins, and cytokine receptors, thus efforts have been focused to modulate its activity. A common observation in diverse experimental systems is that oxidant stress activates NF-κB and antioxidant drugs prevent activation and subsequent inflammatory gene transcription. However, we have recently shown that the inhibitory effect of N-acetylcysteine (NAC) is independent of its role as a substrate of glutathione synthesis and NAC can inhibit Kupffer cell activation at points beyond the initiation of activation. The goal of this study was to characterize the mechanism for NAC-mediated inhibition of Kupffer cell activation. We show for the first time that this process requires a cellular synthetic response to prevent both NF-κB and tumor necrosis factor α (TNF-α) mRNA activation. Furthermore, NAC-mediated inhibition occurs after degradation of IκB-α and nuclear translocation of NF-κB. These data suggest that inhibition of Kupffer cell activation by NAC is a nuclear event and offers a potential approach to modulate Kupffer cell activation during hepatic injury.
Mechanism of inhibition of LPS-induced IL-12p40 production by IL-10 and TGF-β in ANA-1 cells
Authors: Du Caigan , Sriram Subramaniam 
Published: January 2018

Abstract
IL-12, a macrophage-derived proinflammatory cytokine, consists of two polypeptide subunits (p40 and p35) encoded by two separate genes. The p35 subunit is constitutively expressed, whereas the p40 subunit is induced after activation. The bioactive interleukin-12 (IL-12; p70) influences the development of Th1 responses and is a potent activator of natural killer (NK) and T cells. In contrast to IL-12, transforming growth factor β (TGF-β) and IL-10 inhibit production of proinflammatory cytokines, including IL-12, and attenuate Th1-mediated immune response. We have examined the molecular mechanisms by which TGF-β and IL-10 inhibit production of the IL-12p40 subunit in LPS-stimulated murine macrophage cell line. We show that both IL-10 and TGF-β suppress IL-12p40 production by inhibiting the transcription of IL-12p40 gene. At equal concentrations, IL-10 was more potent than TGF-β in inhibiting IL-12p40 gene transcription. TGF-β also reduces the stability of IL-12p40 mRNA, accounting thereby to an additional mechanism of inhibition of IL-12 production. J. Leukoc. Biol. 64: 92–97; 1998.
Macrophage cytoplasmic vesicle pH gradients and vacuolar H+-ATPase activities relative to virus infection
Authors: Natale Valerie A I , McCullough Kenneth C 
Published: January 2018

Abstract
A number of viruses replicate in macrophages, some having an obligate requirement for a macrophage host. This raised the question concerning the role of the macrophage endosomal/lysosomal compartment during such infections. Both lysosomotropic weak bases, amantadine and chloroquine, which interfere with endosomal/lysosomal pH gradients, and the macrolide antibiotic bafilomycin A1, which interferes with vacuolar H+-ATPase, inhibited African swine fever (ASF) virus replication in porcine macrophages. This inhibition was reversible: replenishment of bafilomycin, but not amantadine or chloroquine, maintained the inhibition. The characteristics of the inhibition, and the capacity of virus to escape and re-commence replication, related to the capacity of each drug to interfere with the endosomal/lysosomal proton pump. These results demonstrate that the virus actually requires macrophage endosomal/lysosomal activity for its replication. Therein, vacuolar H+-ATPase activity is particularly critical for successful virus replication, which is interesting considering the importance of this for endosomal/lysosomal activity and macrophage function. J. Leukoc. Biol. 64: 302–310; 1998.
Interleukin-8 priming of human neutrophils is not associated with persistently altered calcium fluxes but is additive with lipopolysaccharide
Authors: van Dervort Alan L , Lam Charles , Culpepper Susan , Tuschil Andrea F , Wesley Robert A , Danner Robert L 
Published: January 2018

Abstract
Interleukin-8 (IL-8) priming was studied in neutrophils to examine its dependency on altered calcium fluxes and for similarity to lipopolysaccharide (LPS). IL-8 caused a rapid rise in [Ca2+]i that returned to baseline values by 20 min. Peak [Ca2+]i transients in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) were unaltered in IL-8-primed compared with unprimed cells. In comparison to LPS and tumor necrosis factor (TNF), IL-8 was a much weaker priming agent as measured by either O2– or H2O2 production. Despite their large disparity in potency, IL-8 and LPS priming were additive using fMLP, a receptor-dependent stimulator, and synergistic using the post-receptor, protein kinase C activator, phorbol 12-myristate 13-acetate (PMA) to trigger the respiratory burst. In contrast, IL-8 and TNF priming were synergistic for fMLP (P = 0.05), but completely nonadditive when PMA was used as the neutrophil stimulant (P = 0.05 for subadditivity). Thus, lasting alterations in [Ca2+]i are not a necessary characteristic of IL-8-primed cells. IL-8 and LPS appear to prime by non-overlapping pathways, whereas IL-8 and TNF appear to share mechanisms distal to protein kinase C activation. IL-8 and LPS may independently contribute to neutrophil-mediated host defense or injury by priming through distinct pathways. J. Leukoc. Biol. 64: 511–518; 1998.
Expression of a structural domain of the β2 subunit essential for αMβ2 ligand recognition
Authors: Goodman Thomas G , DeGraaf Michael E , Fischer H David , Bajt Mary Lynn 
Published: January 2018

Abstract
The β2 leukocyte integrins comprise a group of closely related adhesion receptors that mediate critical events during normal and inflammatory immune responses. Central to the understanding of β2 integrin function is the basis of ligand recognition. Results from our laboratory and others indicate the presence of multiple ligand contact points in both the α and β subunit. As an approach to identify and characterize regulatory domains of the β2 subunit, we have generated two different subdomains of the β2 subunit for expression on the surface of mammalian cells through a phosphatidylinositol glycan anchor. The first subdomain contains the putative β2 MIDAS motif implicated in ligand binding [β2(LB)], whereas the second β2 subdomain contains the cysteine-rich region [β2(CR)]. Cells expressing αm and β2 constructs singly or cotransfected transiently in COS-7 cells were tested for the ability to bind to immobilized iC3b. Cells bearing the recombinant αMβ2(LB) were capable of adhering to iC3b in a manner similar to that observed with the complete αMβ2 heterodimer. In contrast, cells expressing αMβ2(CR) failed to adhere to immobilized iC3b. Moreover, cells bearing singly transfected α or β chains alone failed to adhere to immobilized iC3b. These results indicate that along with αm, the β2(LB) subdomain contains the sufficient components within the β2 subunit essential for ligand recognition. These findings support the hypothesis that the β2 subunit cooperates with site(s) within the αM subunit in a receptor/cation/ligand complex resulting in high-affinity ligand interaction. J. Leukoc. Biol. 64: 767–773; 1998.