bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumoricidal response of liver macrophages isolated from rats bearing liver metastases of colon adenocarcinoma
Authors: Thomas C , Nijenhuis A M , Dontje B , Daemen T , Scherphof G L 
Published: January 2018

Abstract
Iniraportal Inoculation of CC531 adenocarcinoma cells into syngeneic rats causes an increase of liver macrophage cell number but not of major histocompati bility complex class II antigen expression. On day 1 after inoculation of 105 CC531 cells, a fixed number of isolated liver macrophages lysed significantly more target cells in vitro than did control cells. This effect was still present after 4 weeks, A 10-fold higher initial tumor dose sig nificantly suppressed the macrophage response during the first 2 weeks. In contrast to tumoricidal activity induced by lipopolysaccharide in vitro, the tumoricidal response following in vivo challenge with tumor cells appeared not closcly related to the production of reactive nitrogen in termediates, as in the latter case it was not abrogated in the presence of nitric oxide synthase inhibitor. Further more, the liver macrophage population appeared not fully activated after tumor inoculation as lipopolysaccharide further increased tumoricidal activity in vitro. The ob served numerical and functional response of liver macro phages to intraportally inoculated tumor cells points at an important role of these cells in aspecific immune reac tivity aimed at the reduction of local tumor growth. Re sults suggest that mechanistic differences exist between macrophage tumoricidal activity induced by tumor cells as compared with lipopolysaccharide. J. Leukoc. Biol. 57: 617–623; 1995.
Structure-activity relationships of chemokines
Authors: Clark-Lewis Ian , Kim Key-Sun , Rajarathnam Krishnakumar , Gong Jiang-Hong , Dewald Beatrice , Moser Bernhard , Baggiolini Marco , Sykes Brian D 
Published: January 2018

Abstract
Structural analysis of chemokines has revealed that the α/β structural-fold is highly conserved among both the CXC and CC chemokine classes. Although dimerization and aggregation is often observed, the chemokines function as monomers. The critical receptor binding regions are in the NH2-terminal 20 residues of the protein and are the least ordered in solution. The flexible NH2-terminal region is the most critical receptor binding site and a second site also exists in the loop that follows the two disulfides. The well-ordered regions are not directly involved in receptor binding but, along with the disulfides, they provide a scaffold that determines the conformation of the sites that are critical for receptor binding. These general requirements for function are common to all the chemokines. For the CC chemokines, receptor activation and receptor binding regions are separate within the 10 residue NH2-terminal region. This has allowed identification of high affinity analogs that do not activate the receptor and are potent antagonists. J. Leukoc. Biol. 57: 703–711; 1995.
Interleukin-5 and its receptor: a drug target for eosinophilia associated with chronic allergic disease
Authors: Devos René , Plaetinck Geert , Comelis Sigrid , Guisez Yves , Van der Heyden José , Tavemier Jan 
Published: January 2018

Abstract
A characteristic feature of chronic allergic diseases such as asthma is the increase in eosinophil numbers in the inflamed tissue. In light of its specificity for the development of eosinophils, interleukin-5 (IL-5) is considered the most important cytokine involved in the regulation of eosinophilia. Hence, an antagonist for IL-5 activity is a new target for drug discovery programs. We have examined the opportunity for both a random and a rational approach for the identification of such an antagonist. The elucidation of the structure of IL-5 and the initial structure/function analysis of the ligand/receptor complex constitute a first step towards the design of antagonistic compounds. The identification of a small compound by random screening able to inhibit the IL-5/IL-5 receptor interaction indicated an important domain in the receptor. We examine here protein-based IL-5 antagonists, such as IL-5-muteins, soluble IL-5 receptor constructs, and monoclonal antibodies, for their potential as IL-5/IL-5 receptor antagonists, and the use of a murine model of eosinophil airway inflammation for their evaluation. J. Leukoc. Biol. 57: 813–819; 1995.
Cytokine induction by the immunomodulators imiquimod and S-27609
Authors: Testerman Traci L , Gerster John F , Imbertson Linda M , Reiter Michael J , Miller Richard L , Gibson Sheila J , Wagner Tamara L , Tomai Mark A 
Published: January 2018

Abstract
Imiquimod (R-837, S-26308) and the analogue S-27609 were evaluated for cytokine induction in human blood cells. Both compounds induced interferon-α (EFN), tumor necrosis factor-α (TNF), interleukin (IL)-1β, and EL-6 with S-27609 being 5 to 10 times more potent. Imiquimod and S-27609 also induced IL-1α, IL-1 receptor antagonist, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), and macrophage inflammatory protein-1α. The profile of cytokines induced by imiquimod and S-27609 was different from those seen with lipopolysaccharide and polyinosinic-polycytidylic acid. Kinetic studies with both imiquimod and S-27609 revealed induction of cytokines as early as 1-4 h after stimulation. Although most of the cytokines produced by S-27609 were secreted, significant concentrations of IL-1α and BL-1β remained intracellular. Monocytes were largely responsible for the cytokines produced. Finally, S-27609-induced mRNA expression for TNF, IFN, and IL-8, and this induction did not require protein synthesis. Taken together, these studies extend previous findings by showing induction of additional cytokines and providing insight into the mechanism of cytokine induction by these molecules.
Histamine enhances granulocyte-macrophage colony-stimulating factor and interleukin-6 production by human peripheral blood mononuclear cells
Authors: Mor Shlomith , Nagler Arnon , Barak Vivian , Handzel Zeev T , Geller-Bernstein Carmi , Fabian Ina 
Published: January 2018

Abstract
The effect of histamine on the production of cytokines by subpopulations of mononuclear cells was studied. A 3.5-fold increase in the number of myeloid colony-forming units (CFU-C) was observed when bone marrow cells were cultured in the presence of conditioned medium prepared from nonadherent mononuclear cells cultured with 10−4 M histamine (CM-histamine) compared with phosphate-buffered saline (CM-PBS). Using ELISA and radioimmunoassay kits, histamine was found to enhance the production of GM-CSF (9.6-fold) and IL-6 (8.2-fold) by mononuclear cells but not by nonadherent cells or large granular lymphocytes. Anti-GM-CSF and anti-IL-6 antibodies markedly blocked cytokine activity in CM-PBS, whereas the blocking effect in CM-histamine was moderate, indicating enhanced GM-CSF and IL-6 activity in CM-histamine. No GM-CSF or IL-6 levels could be detected in CM-histamine or CM-PBS prepared from CD3+, CD4+, or CD8+ lymphocytes. Preincubation of CM-histamine with H1 and H2 receptor antagonists resulted in complete blocking of the histamine-enhanced colony-stimulating activity. We conclude that histamine is able to activate human mononuclear cells to generate cytokines such as GM-CSF and IL-6 via H1 and H2 receptors.
Unique patterns of regulation of nitric oxide production in fibroblasts
Authors: Lavnikova Natasha , Laskin Debra L 
Published: January 2018

Abstract
The pathways regulating rat and mouse embryonic and lung fibroblast nitric oxide production were analyzed in an attempt to evaluate the potential role of these cells in nonspecific host defense and inflammation. Interleukin-1β (IL-1β) was found to be the strongest single activator in all types of fibroblasts examined. In addition, lipopolysaccharide (LPS) was synergistic with IL-1β or tumor necrosis factor-α (TNF-α) in induction of nitric oxide synthesis. These patterns of responsiveness are not observed in macrophages and may be significant in initiation of early host defense processes, before specific interferon-γ (IFN-γ)–mediated immune responses have become operative. Rat and mouse fibroblasts were also found to produce nitric oxide when primed with IFN-γ and simultaneously treated with IL-1, TNF-α, or LPS. The doses of IFN-γ effective in priming fibroblasts for nitric oxide production were as low as 1-10 U/ml. Furthermore, effective triggering doses of LPS, TNF-α, and IL-1 were 10 ng/ml, 100 U/ml, and 0.2 ng/ml, respectively. These results demonstrate that fibroblasts are activated more readily to produce nitric oxide than interstitial macrophages and may be the major source of this mediator in tissues. Immunohistochemical studies demonstrated that fibroblasts are heterogeneous with respect to inducible nitric oxide synthase expression with the majority of cells not involved in the response. Fibroblasts were also found to be distinct from macrophages in their sensitivity to the suppressive effects of Transforming growth factor-β, which in fibroblasts inhibited both IFN-γ plus LPS–and IFN-γ plus TNF-α-induced nitric oxide production. At the stage of growth crisis, a dramatic increase in nitric oxide production was observed in rat fibroblasts in response to IFN-γ or TNF-α that may be directly correlated with cellular senescence. Taken together, our data suggest that mouse and rat fibroblasts are potential effectors in both IFN-γ-dependent and -independent nitric oxide-mediated processes and that the patterns regulating nitric oxide metabolism in these cells are distinct from those of macrophages.
Dendritic cells and the replication of HIV-1
Authors: Cameron P , Pope M , Granelli-Piperno A , Steinman R M 
Published: January 2018

Abstract
Dendritic cells (DCs) are a distinct lineage of white cells that arise from CD34+ progenitors in the bone marrow. DCs exhibit many specializations that lead to efficient antigen capture and presentation to T cells, both CD4+ helpers and CD8+ killers. In several human tissues, DCs express the CD4 receptor for HIV-1. Some early reports described the explosive infection of blood-derived DCs by HIV-1 and a severe compromise of their presenting function. In contrast, other studies described active HIV-1 replication when DCs were interacting with CD4+ T cells. This productive infection could begin with a low viral burden in DCs but required that the DCs retain their normal binding and stimulatory function for T cells. In this review we first summarize those features of the DC system that seem pertinent to HIV-1 infection. Then we consider the current literature on the interaction of HIV-1 with DCs, from several different tissues, in HIV-1-infected patients or following challenge with HIV-1 in vitro. The literature leads to the hypothesis that HIV-1 infection is a battleground in which DCs could be leading both of the armies, the aggressor that promotes HIV-1 replication from relatively small numbers of infected cells and the defender that mediates T cell-dependent resistance.
ICAM-1 mediates leukocyte-endothelium adhesive interactions in the reversed passive Arthus reaction
Authors: Smith Robert J , Chosay John G , Dunn Colin J , Manning Anthony M , Justen James M 
Published: January 2018

Abstract
A murine anti-rat intercellular adhesion molecule 1 (ICAM-1) monoclonal antibody (mAb), 1A29, was used to investigate the importance of blood leukocyte-associated β2-integrin (CD11/CD18)/vascular endothelmm-associated ICAM-1 adhesive interactions in the reversed passive Arthus reaction (RPAR) in rats. An Arthus pleurisy reaction (4 h) was employed in these studies because it permits the accurate quantitation of polymorphonuclear neutrophil (PMN) influx into the pleural space and fluid accumulation. 1A29, which localized within Arthus lung lesions, caused a dose-dependent (0.5–2.0 mg/kg, i.v.) inhibition of PMN influx (19–56%) and exudate volume (9–55%) in the Arthus pleurisy reaction. P7 (2 mg/kg, i.V.), a murine anti-human P-selectin mAb used as an isotype-matched control tor 1A29, did not localize at the lung lesion site and was inactive. Immunohisto-chemical analysis of lung tissue from 1A29-treated rats demonstrated increased granulocyte accumulation in the alveolar capillaries compared with more extensive granulocyte emigration into the lung tissue and pleural space in P7-treated rats and Arthus control rats; however, quantitative image analysis revealed increased numbers of lung granulocytes in 1A29-treated rats compared with controls. Neither ICAM-1 mRNA nor expression, assessed by immunocytochemistry, was increased above control levels in rats during the pleural Arthus reaction. Neutropenia was not observed in either 1A29- or P7-treated rats.
Protein tyrosine kinases in activation signal of human basophils through the immunoglobulin E receptor type I
Authors: Benhamou Marc , Feuillard Jean , Lortholary Olivier , Bourgeois Clotilda , Michel Laurence , LeGoff Liliane , Michel Ariane , Mencia-Huerta Jean-Michel , Lejeune Françoise , Casassus Philippe , Debré Patrice , Arock Michel 
Published: January 2018

Abstract
Human basophils activated through high-affinity immunoglobulin E (IgE) receptors (FcRI) are involved in the late phase of the allergic reaction. To investigate the possible involvement of protein-tyrosine kinases in this activation we used human acute basophilic leukemia (ABL) cells in culture as well as a pure population of normal basophils in vitro-derived from human bone marrow precursor cells (HBMB). ABL cells were 50–80% basophils at various stages of maturation as assessed by staining, morphology, ultrastructure, and flow cytometry analysis, and only basophils in ABL cells expressed FcRI. Aggregation of FcRI by IgE and anti-IgE, IgE and antigen, or anti-FcRI monoclonal antibodies on ABL cells or on HBMB, led to increased tyrosine phosphorylation of 120-, 100-, 80-, 72-, 50- to 65-, and 38-kDa substrates. Tyrosine phosphorylations in ABL cells were in basophils because 1) they were detected after a 5-s stimulation, 2) they were observed under conditions where mediator release is minimal, i.e., in the absence of extracellular calcium, 3) hapten addition during antigen stimulation resulted in almost total disappearance of tyrosine phosphorylations within 30 s. There was correlation between histamine release and tyrosine phosphorylation in anti-IgE dose-responses and in dose-responses of the tyrosine kinase inhibitor genistein. The tyrosine kinase p72syk was detected in the cells. Stimulation of ABL cells for 1 min resulted in extracellular calcium-independent tyrosine phosphorylation and activation of p72syk Therefore, tyrosine kinases are involved in the early steps of human FcRI signaling in basophils. Tyrosine kinases and their substrates could represent new potential therapeutic targets to prevent the development of the allergic reaction. 1996.
Alveolar macrophage kinetics and multinucleated giant cell formation after lung injury
Authors: Prieditis H , Adamson I Y R 
Published: January 2018

Abstract
Multinucleated giant cells (MGC) are a prominent feature of some chronic inflammatory states in the lung. These cells are formed by macrophage fusion, but how this process relates to the kinetics of alveolar macrophage (AM) production and proliferation is not clear. In this serial study, we compare AM kinetics and MGC formation after instilling carbon, silica, asbestos, bleomycin, and saline into the lungs of mice. Animals were killed up to 16 weeks later with [3H]thymidine injected 1 h before death. Counts of AM and MGC were carried out after bronchoalveolar lavage, and cell labeling was assessed by autoradiography. All test substances induced an inflammatory response with equal AM numbers recovered up to 2 weeks. Subsequently, the number returned to normal after carbon but remained elevated in the other groups. After carbon the lung structure was normal, there was no increase in AM label, and no MGC formed. Bleomycin-injected lungs progressed to fibrosis with only a brief, small increase in AM labeling and no MGC formation. After silica, and particularly asbestos, the lungs showed fibrosis, and many granulomas with large MGC were seen. Lavaged AM from these lungs showed a significant increase in DNA synthesis after 2 weeks, followed by higher numbers of MGC, none of which were labeled. Labeled AM tended to be free of particles, whereas MGC after 4 weeks contained many particles. The results indicate a relationship between AM proliferation and fusion, whereby AM growth appears to be prerequisite for cell fusion and MGC formation as a feature of granulomatous disease.
Estrogen regulation of JE/MCP-1 mRNA expression in fibroblasts
Authors: Kovacs E J , Faunce D E , Ramer-Quinn D S , Mott F J , Dy P -W W , Frazier-Jessen M R 
Published: January 2018

Abstract
We have recently demonstrated that 17β-estradiol (E2) inhibits peritoneal adhesion formation. Because macrophages play a central role in inflammation and wound healing, we chose to investigate whether the E2 could inhibit the expression of JE, the murine monocyte chemoattractant protein-1 (MCP-1). To accomplish this, murine fibroblasts were cultured with physiological concentrations of E2 (3–300 pg/ml) with or without inducers of JE/MCP-1 mRNA expression. Untreated cells failed to express the message, but, following stimulation, a marked increase in JE/MCP-1 mRNA expression was observed. At 10–30 pg/ml, E2 had no effect on JE/MCP-1 mRNA expression in stimulated fibroblasts. In contrast, lower and higher doses of E2 inhibited the expression of JE/MCP-1 mRNA in stimulated fibroblasts. Treatment with tamoxifen reversed the E2-inhibition of expression of the message. These data demonstrate that JE/MCP-1 mRNA expression is controlled, in part, by estrogen and suggest that macrophage recruitment may be affected by circulating levels of E2.
Transcriptional regulation of LDL receptor-related protein by IFN-γ and the antagonistic activity of TGF-β1 in the RAW 264.7 macrophage-like cell line
Authors: Hussaini Isa M , LaMarre Jonathan , Lysiak Jeffrey J , Karns Larry R , VandenBerg Scott R , Gonias Steven L 
Published: January 2018

Abstract
Low density lipoprotein receptor-related protein (LRP) is a major receptor for multiple ligands, including chylomicron and VLDL remnants, bacterial toxins, viruses, proteinases, lipoprotein lipase, and activated α2-macroglobulin (α2M). In this study, we used Northern blot analyses and nuclear run-on experiments to demonstrate that interferon-γ (IFN-γ) causes a concentration-dependent decrease in steady-state LRP mRNA expression and gene transcription rate in RAW 264.7 cells. IFN-γ also markedly increased expression of inducible nitric oxide synthase (NOS), as expected; however, the increase in nitric oxide was not responsible for the down-regulation of LRP expression since the NOS inhibitor, NG-monomethyl-l-arginine, did not preserve LRP expression in IFN-γ-treated cells. Trans-forming growth factor-β1 (TGF-β1; 2.5 ng/mL) had no independent effect on LRP expression and did not modify the response to IFN-γ when the two cytokines were added simultaneously to cultures. When TGF-β1 was added 24 h prior to IFN-γ, the extent of LRP down-regulation was significantly reduced. Specific binding of the LRP ligand, activated 125I-α2M, was decreased by 76 ± 5% in cells treated with 100 U/mL IFN-γ, but only by 45 ± 7% in cells treated with 100 U/mL IFN-γ after TGF-β1-pretreatment. The antagonistic activity of TGF-β1 on the IFN-γ response in RAW 264.7 cells did not result from a change in LRP mRNA stability or IFN-γ receptor expression, as determined by Northern blot analyses 125I-IFN-γ binding experiments. The studies presented here suggest that the balance between IFN-γ and TGF-β1 may be critical in determining LRP expression at sites of infection and inflammation.
Regulation of leukocyte adhesion and signaling in inflammation and disease
Authors: Wahl S M , Feldman G M , McCarthy J B 
Published: January 2018

Abstract
Cell adhesion molecules provide the foundation for cell communication, trafficking, and immune surveillance central to host defense. These adhesion molecules which include selecting, integrins and members of the Ig superfamily, provide a recognition system between leukocytes, endothelial cells and matrix molecules. Leukocyte-endothelial interactions initiate recruitment at sites of injury, infection and inflammation. Cell-cell and cell-matrix interactions also influence leukocyte phenotype and function. Dysregulation of these adhesion and signal transduction pathways can contribute to continued recruitment and persistent leukocyte activation with unresolved inflammation. Based on the pivotal role adhesive interactions play, the adhesion molecules provide potential targets for intervention. Selected synthetic fibronectin peptides, which inhibit leukocyte integrin binding and signal transduction in vitro, block recruitment and activation to limit inflammation in vivo.
Human recombinant monocyte chemotactic protein and other c-c chemokines bind and induce directional migration of dendritic cells in vitro
Authors: Xu Luo Ling , Warren M Kim , Rose Wendy L , Gong Wanghua , Wang Ji Ming 
Published: January 2018

Abstract
Because dendritic cells (DC) are the most potent antigen-presenting cells involved in many pathophysiological responses, we investigated the effect of chemokines on the migration of these cells in an effort to determine whether chemokines may contribute to the initiation of immune responses. CD34+ progenitor cells isolated from umbilical cord blood were grown in suspension cultures with cytokines and expanded 50- to 100-fold. A variable proportion of the cells expressed markers consistent with DC. The proportion of CD1a+ DC was increased when the cells were cultured with interleukin-4 (IL-4). These cells expressed specific binding sites for C-C and C-X-C chemokines. Cells cultured with or without IL-4 had similar binding profiles. All C-C chemokines tested, including monocyte chemotactic protein (MCP)-1, MCP-2, MCP-3, macrophage inflammatory protein-1α (MIP1α), MIP-1β, and RAN-TES, induced migration of DC-enriched cells cultured with or without IL-4 with MCP-3 being the most potent chemoattractant. Phenotypic analysis of cell migrating in response to C-C chemokines showed that CD1a+ cells were indeed attracted across the polycarbonate filters, and there was no preferential attraction of contaminating CD14+ monocytes by C-C chemokines. DC-enriched cells also expressed specific binding sites for IL-8 and NAP2, which failed to induce cell migration. Our results suggest that C-C chemokines may participate in the recruitment of DC to amplify host defense.
Integrin signaling in leukocytes: lessons from the α6β1 integrin
Authors: Wei Jueyang , Shaw Leslie M , Mercurio Arthur M 
Published: January 2018

Abstract
The adhesive interactions of leukocytes with basement membrane components and other extracellular matrix (ECM) proteins are mediated largely by the integrin family of receptors. These interactions can be regulated by various effector molecules including chemokines, growth factors, and other cell surface proteins by a mechanism termed inside-out signaling of integrin function. On engagement by their ligands, integrins activate a wide range of signaling pathways that regulate a broad array of leukocyte functions such as chemotaxis, cytokine responsiveness, phagocytosis, and gene expression. This review highlights recent advances in the understanding of integrin signaling in leukocytes with an emphasis on our own work on the α6β1 integrin, the major laminin receptor expressed by these cells.