bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell rescue of monocytes from apoptosis: role of the CD40-CD40L interaction and requirement for CD40-mediated induction of protein tyrosine kinase activity
Authors: Suttles Jill , Evans Mike , Miller Robert W , Poe Jonathan C , Stout Robert D , Wahl Larry M 
Published: January 2018

Abstract
Circulating monocytes have a limited life span and will undergo apoptosis in the absence of specific stimuli. Recent studies have demonstrated that monocytes can be rescued from apoptosis via lipopolysaccharide (LPS) activation or stimulation with interleukin-1 or tumor necrosis factor-α. Based on previous studies from our laboratory, we hypothesized that, in nonseptic (e.g., autoimmune) inflammation, the presence of activated T cells may enhance monocyte longevity through T cell contact-dependent signaling. Plasma membranes prepared from 6 h activated (TmA) and resting (TmR) purified CD4+ T cells were added to resting elutriation-purified monocytes cultured in serum-free medium. Cells were assayed for degree of apoptosis occurring over a 72-h incubation using both agarose gel electrophoresis and flow cytometry. The addition of TmA (but not TmR) was capable of blocking monocyte apoptosis and the ability of TmA to rescue monocytes was abrogated by the addition of anti-CD40L antibodies. Rescue of monocytes from apoptosis could also be mediated by direct cross-linking of monocyte CD40. Inhibitors of tyrosine kinase activity blocked both TmA and anti-CD40-mediated rescue of monocytes from apoptosis, suggesting a primary role of a tyrosine kinase signaling pathway in the events controlling monocyte longevity.
MIP-1α contributes to the anticryptococcal delayed-type hypersensitivity reaction and protection against Cryptococcus neoformans
Authors: Doyle Hester A , Murphy Juneann W 
Published: January 2018

Abstract
Leukocyte infiltration into infected tissues is essential for the clearance of microorganisms. In animals with a cell-mediated immune (CMI) response to the infectious agent, as opposed to naive animals, leukocyte migration is greatly enhanced into sites of the organism or antigen. The role of the chemotactic cytokine or chemokine, macrophage inflammatory protein-1α (MIP-1α), in the expression phase of the CMI response and in protection against Cryptococcus neoformans was assessed. With the use of a gelatin sponge model in mice as a means of detecting an anti-cryptococcal delayed-type hypersensitivity (DTH) reaction, we found that MIP-1 α levels in fluids from cryptococcal antigen (CneF)-injected sponges in immunized mice (DTH-reactive sponges) were significantly increased over levels of MIP-1α in fluids from saline-injected control sponges at 12 and 24–30 h after injection. MIP-1α levels peaked before increases in neutrophils and lymphocytes in the DTH-reactive sponges, suggesting that MIP-1α was responsible, at least in part, for attracting these leukocyte types. Immunized mice treated with neutralizing antibody to MIP-lα before sponge injection with CneF had reduced numbers of neutrophils and lymphocytes in the DTH-reactive sponges and showed reduced clearance of C. neoformans from the lungs, spleens, livers, and brains when compared with controls. Furthermore, injection of rmMIP-1α into sponges in naive mice resulted in an increase in the influx of neutrophils and lymphocytes into the sponges compared with saline-injected sponges. Together our findings provide solid evidence that MIP-1α is a component of the anticryptococcal DTH reaction. In addition, MIP-1α influences neutrophil influx and attracts lymphocytes into the DTH reaction site. Finally, we showed that MIP-1α plays a role in protection against C. neoformans.
Monocytes/macrophages rather than PMN are involved in early cartilage degradation in cationic immune complex arthritis in mice
Authors: van Lent P L E M , Blom A , Holthuysen A E M , Jacobs C W M , van De Putte L B A , van Den Berg W B 
Published: January 2018

Abstract
We investigated the involvement of polymorphonuclear granulocytes (PMN) and monocytes in cartilage degradation in immune complex-mediated arthritis (ICA). ICA induced with lysozyme-anti-lysozyme in the murine knee joint is characterized by a major influx of PMNs followed by monocytes and marked cartilage proteoglycan (PG) depletion develops within 2 days. Around 60% of 35S-prelabeled PG is lost at day 2. Influx of cells was manipulated using interleukin-1 (IL-1) receptor antagonist (IL-lra) or anti-bodies to adhesion molecules. Cellular infiltrate was analyzed on hematoxylin-stained joint sections. Early systemic treatment with IL-lra highly reduced PMN influx, whereas monocyte influx was hardly diminished. PG loss was not significantly reduced, declining from 62% in controls to 47% in IL-lra-treated mice. Total blockade of cell influx was found after intravenous treatment with monoclonal antibodies 5C6 (anti-CD11b/CD18:anti-CR3) or NIMP.R14 (25–30 kDa protein mainly present on PMN) and PG loss was reduced to 5–10%. A similar reduction was observed after prior depletion of circulating PMNs with total body irradiation. Because amounts of IL-1 produced in leukopenic and control arthritic joints are comparable, this suggests that IL-1 is only marginally involved in PG loss in the first phase of ICA. This study indicates that monocytes rather than PMN might be involved in PG loss in this form of arthritis, either directly or by local activation of synovial layer cells of the joint.
Monocyte chemotactic protein-4: tissue-specific expression and signaling through CC chemokine receptor-2
Authors: Godiska Ronald , Chantry David , Raport Carol J , Schweickart Vicki L , Le Trong Hai , Gray Patrick W 
Published: January 2018

Abstract
Chemokines constitute a family of low-molecular-weight proteins that attract or activate a variety of cell types, including leukocytes, endothelial cells, and fibroblasts. An electronic search of the GenBank Expressed Sequence Tags database uncovered a partial cDNA sequence with homology to the chemokine monocyte chemotactic protein-1 (MCP-1). Isolation of the full-length clone revealed that it encodes the chemokine MCP-4, an eosinophil chemoattractant recently described by Uguccioni et al. [J. Exp. Med. 183, 2379–2384]. Recombinant MCP-4 was expressed in mammalian cells and purified by heparin-Sepharose chromatography. Sequencing the amino terminus of this protein corroborated the reported sequence of recombinant MCP-4 produced in insect cells. As shown by calcium flux assays, MCP-4 activated the cloned G protein-coupled receptor CCR-2, which also recognizes MCP-1 and MCP-3. Northern hybridization indicated that MCP-4 is constitutively expressed at high levels in the small intestine, colon, and lung. This expression profile is consistent with its role as a chemoattractant for eosinophils, which can be rapidly mobilized to the lung or intestine in response to invading pathogens. In marked contrast to MCP-1, MCP-4 was not induced in cell lines treated with pro-inflammatory stimuli such as lipopolysaccharide or tumor necrosis factor α.
Inflammatory damage following first-generation replication-defective adenovirus controlled by anti-LFA-1
Authors: Guérette B , Moisset P-A , Huard C , Tardif F , Gravel C , Tremblay J P 
Published: January 2018

Abstract
First-generation replication-defective adenoviruses have been reported to lead to transient reporter gene expression due to a specific immune reaction involving T and B lymphocytes. Some recent reports have also demonstrated the presence of a nonspecific inflammatory reaction involving macrophages and neutrophils after both intramuscular injections and viral vectors transduction. To further investigate this nonspecific inflammatory reaction, ΔE1/E3a adenoviruses were injected intramuscularly in immunocompetent mice. Some of these mice were treated with anti-LFA-1. The adenovirus-injected muscles showed abundant CD4+, CD8+, LFA-1+, and Mac-1+ cell infiltration 3 days after the ΔE1/E3a injection. The anti-LFA-1 monoclonal antibody was able to block the nonspecific inflammatory damage due mostly to neutrophils and macrophages. The anti-LFA-1 did not produce this effect by reducing the muscle infiltration by LFA-1+ cells. It may instead have blocked the direct interaction between LFA-1 and ICAM-1 thus preventing the damage produced by the respiratory burst of neutrophils. Blocking the resulting damage of this inflammatory reaction with anti-LFA-1 in animals also treated with FK506, a powerful immunosuppressant for gene therapy, largely increased the long-term transgene expression compared with mice only treated with FK506.
Inhibitory effect of 3,4-dichloropropionaniline on cytokine production by macrophages is associated with LPS-mediated signal transduction
Authors: Xie Y C , Schafer R , Barnett J B 
Published: January 2018

Abstract
Our previous studies demonstrated that both in vivo and in vitro 3,4-dichloropropionanilide (propanil) exposure inhibited interleukin-6 (IL-6) and tumor necrosis factor (TNF) production by adherent thioglycollate-elicited peritoneal cells (macrophages) after lipopolysaccharide (LPS) stimulation. In this study, we report that IL-6 and TNF-α message is reduced by propanil in a concentration-dependent pattern, yet the stability of cytokine mRNA is not affected. In addition, exposure of macrophages to propanil after a relatively short period of LPS stimulation significantly reduced the production of IL-6 and TNF. Determination of the intracellular Ca2+ levels demonstrates that LPS-induced Ca2+ release is abrogated in propaniltreated macrophages. However, the binding of LPS to macrophages is not affected. Measurement of inositol 1,4,5-triphosphate (IP3) demonstrates that propanil significantly increases the level and the duration of IP3 in macrophages. These results suggest that the inhibitory effect of propanil on macrophage cytokine production is associated with the early stages of LPS-mediated signal transduction in macrophages.
Modulation of human neutrophil inflammatory responses by nitric oxide: studies in unprimed and LPS-primed cells
Authors: Nath Jayasree , Powledge Annette 
Published: January 2018

Abstract
Because nitric oxide (NO) can act both as a regulatory and as a toxic molecule, we have studied N-formyl-methionyl-leucyl-phenylalanine (fMLF) -stimulated responses of human neutrophils (PMNs) during various conditions of NO modulation in unprimed and bacterial lipopolysaccharide (LPS) -primed cells. Effects of various NO modulators were assessed on stimulated superoxide (O2-) generation, granule exocytosis, homotypic aggregation, and rises in intracellular free Ca2+ ([Ca2+]i). Significant differences in the effects of various NO modulators on inflammatory responses of PMNs kept in stirred suspension versus those kept under static and/or adherent conditions, were observed. L-arginine, the physiological substrate for NO synthase (NOS), and NG-nitro-L-arginine methyl ester, an inhibitor of NOS, both caused a 40-50% inhibition of LPS-induced priming of O2- generation in PMNs in stirred suspension, but not in LPS-primed PMNs under static or adherent conditions. The NO donors, sodium nitroprusside and S-nitroso-N-acetylpenicillamine, completely abrogated the LPS-induced priming of 02- generation in PMNs in suspension, while causing only a 40-50% inhibition in PMNs under static or adherent conditions. The Ca2+ ionophore, A23187, prevented the LPS-induced priming of 02-generation without affecting 02- generation in unprimed PMNs. LPS priming of PMNs induced about a twofold increase in fMLF-stimulated homotypic aggregation, exocytosis of secondary granules, and rises in [Ca2+]i. In related studies, we also provide definitive evidence for enzymatic formation of NO in human PMNs and demonstrate a significant decrease in NO levels in LPS-primed PMNs. Taken together, these findings indicate that NO modulates PMN inflammatory responses and plays a protective role in priming and activation processes of inflammatory PMNs.
Monocyte chemoattractant protein-2 is a potent agonist of CCR2B
Authors: Moore Una M , Kaplow June M , Pleass Robert D , Castro Sandra W , Naik Kuni , Lynch Carolyn N , Daly Steven , Roach Alan G , Jaye Michael , Williams Robert J 
Published: January 2018

Abstract
The binding and functional activity of the CC chemokines monocyte chemoattractant protein-1 (MCP-1), MCP-2, and MCP-3 have been characterized using Chinese hamster ovary DXB-11 cells transfected with the chemokine receptor CCR2B. Receptor binding studies demonstrated that 125I-labeled MCP-1 bound to a single class of high-affinity receptors with a Kd of 0.14 (0.070.32) nM. In competition studies MCP-1, MCP-2, and MCP-3 completely inhibited 125I-labeled MCP-1 binding with Ki values of 0.3 (0.16-0.46), 8.8 (3.4-26), and 12.2 (0.6-22) nM, respectively. In calcium mobilization studies, MCP-1 and MCP-3 induced robust elevations in intracellular calcium concentrations, whereas MCP-2 was only weakly active. In contrast, using changes in extracellular acidification rate as a functional readout, all three chemokines were identified as potent agonists of CCR2B. These data demonstrate that MCP-2, in addition to MCP-1 and MCP-3, is a potent agonist of CCR2B and furthermore that MCP-2 activates either different or a subset of the signaling pathways activated by MCP-1 and MCP-3.
IL-4 secretion and histamine release by human basophils are differentially regulated by protein kinase C activation
Authors: Schroeder John T , Howard Brian P , Jenkens M Kathleen , Kagey-Sobotka Anne , Lichtenstein Lawrence M , MacGlashan Donald W 
Published: January 2018

Abstract
The role of protein kinase C (PKC) activation was investigated in the secretion of interleukin-4 (IL-4) protein by human basophils. Phorbol myristate acetate (PMA) induced little to no detectable IL-4 protein in culture supernatants, despite being a potent secretagogue of histamine release by basophils. In fact, the secretion of IL-4 by basophils stimulated with ionomycin alone was down-regulated (30-70%) with the simultaneous addition of PMA. In peripheral blood lymphocytes (PBL), however, the combination of ionomycin and PMA were highly synergistic, resulting in maximum IL-4 release but at a slower rate. PKC inhibitors reversed these effects on IL-4 secretion. In sharp contrast to its inhibitory effect on IL-4 protein secretion, PMA did not block the accumulation of IL-4 mRNA in basophils activated by ionomycin. These data suggest that there are marked differences in the regulatory processes for IL-4 transcription, translation, or secretion between basophils and lymphocytes.
Role of complement in in vitro and in vivo lung inflammatory reactions
Authors: Czermak Boris J , Lentsch Alex B , Bless Nicolas M , Schmal Hagen , Friedl Hans Peter , Ward Peter A 
Published: January 2018

Abstract
Complement is one of the integral buttresses of the inflammatory response. In addition to host defense activities, proinflammatory properties of several complement components are described. This overview elucidates the role of complement in inflammatory reactions in vitro and in vivo, focusing on the complement activation products, C5a, and the membrane attack complex, C5b-9. Using several approaches, the impact of these complement components in mechanisms relevant to neutrophil recruitment is emphasized. In addition, the participation of complement in endothelial superoxide generation and its essential requirement for full expression of lung injury is demonstrated, as are the involved intracellular signal transduction pathways. Understanding the mechanisms of complement-induced proinflammatory effects may provide a basis for future therapeutic blockade of complement and/or its activation products. J. Leukoc. Biol. 64: 40–48; 1998.
Complex high affinity interactions occur between MHCI and superantigens
Authors: Chapes Stephen K , Herpich Angela R 
Published: January 2018

Abstract
Staphylococcal enterotoxins A and C1 (SEA or SEC1) bound to major histocompatibility-I (MHCI) molecules with high affinity (binding constants ranging from 1.1 μM to 79 nM). SEA and SEC1 directly bound MHCI molecules that had been captured by monoclonal antibodies specific for H-2Kk, H-2Dk, or both. In addition, MHCI-specific antibodies inhibited the binding of SEC1 to LM929 cells and SEA competitively inhibited SEC1 binding; indicating that the superantigens bound to MHCI on the cell surface. The affinity and number of superantigen binding sites differed depending on whether MHCI was expressed in the membrane of LM929 cells or whether it was captured. These data support the hypothesis that MHCI molecules can serve as superantigen receptors. J. Leukoc. Biol. 64:587–594; 1998.
Oxidized LDL modulates activation of NFκB in mononuclear phagocytes by altering the degradation of IκBs
Authors: Hamilton Thomas A , Major Jennifer A , Armstrong David , Tebo Julie M 
Published: January 2018

Abstract
Oxidized low density lipoprotein (oxLDL) is known to alter the expression of inflammatory gene products in mononuclear phagocytes. The mechanisms involved in this effect were studied by examining the activation of nuclear factor κB (NFκB), a transcription factor known to be important in controlling the expression of such genes. Pretreatment of peritoneal macrophages with oxLDL modulated the activation of NFκB in response to either lipopolysaccharide (LPS) or the combination of interferon-γ (IFN-γ) and interleukin-2 (IL-2). In macrophages pretreated with oxLDL the nuclear translocation of Rel family members (RelA and c-Rel) is delayed (LPS) or markedly diminished (IFN-γ/IL-2) and results in delayed or reduced appearance of κB binding activity within the nucleus. These changes in NFκB activation result from alterations in the stimulus-dependent degradation of IκBα and IκBβ. The effects of oxLDL on NFκB activation depend both on the degree of LDL oxidation (most potent with extensive oxidation) and on the time of exposure of the cells to the lipoprotein preparation (a minimal exposure of 6 h is required before inhibitory effects are observed). The modulation of IκB/NFκB function in cells exposed to oxLDL appears to be responsible for previously reported effects of oxLDL on chemoattractant cytokine gene expression where both inhibition and delay of such stimulus-dependent events has been observed. J. Leukoc. Biol. 64: 667–674; 1998.
Evaluation of the expression of human CAP18 gene during neutrophil maturation in the bone marrow
Authors: Nagaoka Isao , Hirata Michimasa , Sugimoto Koichi , Tsutsumi-Ishii Yuko , Someya Akimasa , Saionji Katsu , Igari Jun 
Published: January 2018

Abstract
To understand the gene expression of CAP18 (18-kDa cationic antibacterial protein), a member of cathelicidins, we evaluated mRNA and protein expression of CAP18 using human bone marrow cells and mature neutrophils. Northern blot analysis revealed that CAP18 mRNA was expressed more abundantly in bone marrow cells than mature neutrophils, whereas Western blot analysis indicated that CAP18 protein was more abundant in mature neutrophils than bone marrow cells. Consistent with this, in situ hybridization using bone marrow cells demonstrated that the expression of CAP18 mRNA was neutrophil lineage-specific and was observed primarily in myelocytes (&gt;95%) with limited expression in more immature cells (promyelocytes) and mature cells (metamyelocytes, band cells, and segmented neutrophils). Furthermore, immunohistochemical study indicated that, coincident with the increase of CAP18 mRNA levels, CAP18-positive cells increased markedly at myelocyte stage, and the increased levels remained almost constant (&gt;95%) in metamyelocytes, band cells, and segmented neutrophils, although the mRNA levels were remarkably reduced in these cells. Together these observations indicate that CAP18 gene transcription likely occurs lineage- and stage-specifically at the myelocyte stage of neutrophil maturation in the bone marrow and results in the synthesis and cytoplasmic accumulation of CAP18, which is present in the subsequent stages of neutrophil maturation. J. Leukoc. Biol. 64:845–852; 1998.
Cytolysis of human dendritic cells by autologous lymphokine-activated killer cells: participation of both T cells and NK cells in the killing
Authors: Parajuli Prahlad , Nishioka Yasuhiko , Nishimura Naoki , Singh Sukh Mahendra , Hanibuchi Masaki , Nokihara Hiroshi , Yanagawa Hiroaki , Sone Saburo 
Published: January 2018

Abstract
Dendritic cells (DC) play a key role in the initiation of immune response by stimulating the naive T cells. The fate of DC after the initiation of immune response is not clearly understood. Although there are few reports implicating natural killer (NK) cells in the elimination of DC, killing of DC by LAK cells, and specifically by T cells, has not been studied. In this study, we observed that DC, generated from monocytes, in vitro in the presence of granulocyte-macrophage colony-stimulating factor, interleukin-4 (IL-4), and tumor necrosis factor α were susceptible to cytolysis by lymphokine-activated killer (LAK) cells induced in the presence of IL-2 and IL-15 but not IL-12 alone. However, LAK cells induced by a combination of IL-12 and suboptimal dose of IL-2 were cytotoxic to DC. When purified lymphocytes were activated with IL-2, the CD8+/CD57− fraction (T-LAK), but not the CD8−/CD57+ fraction (NK-LAK) was cytotoxic to autologous DC. However, when unseparated peripheral blood mononuclear cells were used to generate LAK cells, both T-LAK and NK-LAK fractions showed equal cytotoxicity against autologous DC. Monoclonal antibodies against CD54, CD11a, and CD18 significantly inhibited the cytolysis, indicating that the killing involves the engagement of CD54 with its ligands. J. Leukoc. Biol. 65: 764–770; 1999.
Ubiquitin-proteasome system is involved in induction of LFA-1/ICAM-1-dependent adhesion of HL-60 cells
Authors: Katagiri Koko , Yokosawa Hideyoshi , Kinashi Tatsuo , Kawashima Seiichi , Irie Shinkichi , Tanaka Keiji , Katagiri Takuya 
Published: January 2018

Abstract
Membrane-permeable proteasome inhibitors, lactacystin (LC) and N-acetyl-Leu-Leu-norleucinal (ALLN), but not calpain inhibitor Z-Leuleucinal (ZLL), prevented LFA-1/ICAM-1-dependent cellular adhesion of TPA-stimulated HL-60 cells. These proteasome inhibitors affected neither the induction of monocytic differentiation nor the accompanying protein-tyrosine phosphorylation. They suppressed the increase in the avidity of LFA-1 to ICAM-1 without changing the expression of these molecules. Immunoblotting using monoclonal antibody FK-1, which reacts specifically with polyubiquitinated proteins, demonstrated that the proteasome inhibitors caused the drastic accumulation of the polyubiquitinated proteins in the membrane fraction of TPA-treated HL-60 cells. This indicates that accompanying activation of LFA-1, TPA induces the polyubiquitination of the membrane proteins, which are rapidly degraded by proteasomes. These data taken together show that proteolysis mediated by the ubiquitin-proteasome system is a prerequisite for the induction of LFA-1-dependent adhesion of HL-60 cells. J. Leukoc. Biol. 65: 778–785; 1999.