bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterologous desensitization of IL-8-mediated chemotaxis in human neutrophils by a cell-binding fragment of fibronectin
Authors: Stanton Kimberly J , Frewin Mary Beth , Gudewicz Paul W 
Published: January 2018

Abstract
In this study, we have explored the mechanism for the desensitization of IL-8-mediated neutrophil chemotaxis by a cell-binding fragment of fibronectin (120-kDa FN). Preincubation of neutrophil suspensions with the 120-kDa FN fragment resulted in a heterologous desensitization of IL-8-mediated chemotaxis while not affecting neutrophil chemotaxis to either fMLP or zymosan-activated serum. Preincubation of neutrophils with the βx-integrin-activating antibody (TS2/16) mimicked the effects of the 120-kDa FN fragment while preincubating neutrophils with the β1-integrin blocking antibody (mAb13) abrogated the inhibitory effects of the 120-kDa FN fragment on IL-8-mediated chemotaxis. Furthermore, we also demonstrated that the 120-kDa FN fragment did not inhibit chemotaxis to the CXC chemokine MGSA/GROα which interacts with high affinity to the IL-8 receptor B (CXCR2). By in vivo phosphorylation of neutrophils and probing lysates with an anti-CXCR1 antibody, we demonstrated that the addition of the cell-binding fragment of fibronectin resulted in a time-dependent phosphorylation of CXCR1. These findings suggest that the mechanism of heterologous desensitization of IL-8-mediated chemotaxis following ligation of FN-dependent integrins is the result of phosphorylation of the CXCR1 receptor. J. Leukoc. Biol. 65: 515–522; 1999.
Dendritic cell differentiation pathways of CD34+ cells from the peripheral blood of head and neck cancer patients
Authors: Lathers Deanne M R , Lubbers Eve , Wright Mark A , Young M Rita I 
Published: January 2018

Abstract
Patients with head and neck squamous cell carcinoma (HNSCC) have increased levels of immune-suppressive peripheral blood CD34+ cells. This study showed that the peripheral blood CD34+ cells of HNSCC patients are capable of differentiating into dendritic cells. Because CD34+ cells can differentiate through several pathways into dendritic cell subpopulations, the intermediate cells through which the blood CD34+ cells of HNSCC patients differentiate were identified. After 6–7 days of culturing the CD34+ cells of HNSCC patients with granulocyte-macrophage colony-stimulating factor, stem cell factor, and tumor necrosis factor α, there appeared CD14+CD1a+ and a lesser proportion of CD14−CD1a+ cells resembling the precursor cells of the bipotential and committed dendritic cell differentiation pathways that have been described for cord blood CD34+ cells. To functionally analyze whether these populations were in fact precursor cells, they were isolated and cultured for an additional 10–12 days. Each of these populations was shown to function as precursor cells because they were able to develop into cells that resembled dendritic cells, al though a higher proportion developed from the CD14−CD1a+ cells. In contrast, expression of the dendritic activation/maturation marker CD83 was highest on the cells that developed from CD14+CD1a+ cells. Thus, the CD34+ cells whose levels are increased in HNSCC patients can develop into both committed and bipotential dendritic precursor cells, which can subsequently give rise to dendritic cells. J. Leukoc. Biol. 65: 623–628; 1999.
Superantigens augment antigen-specific Th1 responses by inducing IL-12 production in macrophages
Authors: Bright John J , Xin Zhicheng , Sriram Subramaniam 
Published: January 2018

Abstract
Superantigens (SAg) are microbial proteins that mediate antigen-presenting cell (APC)-T cell interaction by cross-linking MHC class II molecules with subsets of TcRVβ. SAgs are implicated in the pathogenesis of several infectious, inflammatory, and autoimmune diseases. In this study, we examined the influence of SEB on interleukin-12 (IL-12) production and the activation of antigen-specific Th1 responses. Addition of SEB augmented the antigen-induced proliferation of HS-17, a murine MBPp91-103 peptide-specific TcRVβ6+ CD4+ Th1 clone. SEB augments HS-17 T cell proliferation through its interaction with IAs molecules on macrophages, but not with the TcRVβ6 on HS-17 cells. On binding to IAs, SEB induces IL-12 production in macrophages, which in turn augments antigen-induced proliferation of HS-17 T cells. Treatment with anti-IAs mAb 10-3.6 inhibited the antigen- and SEB-induced IL-12 production and T cell proliferation. These results suggest that SAgs augment antigen-specific T cell responses by inducing IL-12 production in macrophages. J. Leukoc. Biol. 65: 665–670; 1999.
Monocyte CD14: a multifunctional receptor engaged in apoptosis from both sides
Authors: Heidenreich Stefan 
Published: January 2018

Abstract
Like all other immune system cells, monocytes and macrophages may undergo apoptotic cell death in response to specific triggers and mediators or as a consequence of aging. However, factors inducing apoptosis and the involved cellular and molecular mechanisms are much better investigated and understood for lymphocytes. Th2 cell-derived cytokines such as interleukin-4 (IL-4) are able to induce monocyte apoptosis most effectively. This process is preceded by down-regulation of the CD14 surface receptor. Mediators such as lipopolysaccharide (LPS) suppress and postpone apoptosis in parallel with up-regulation of CD14. Macrophages are rather resistant against apoptotic damage, and factors able to evoke apoptosis in monocytes are often ineffective in macrophages. Resistance of macrophages against apoptotic triggers may be beneficial for inflammatory processes where macrophages are engaged and needed as phagocytes for ingestion and removal of moribund cells. The multifunctional CD14 receptor of monocytes/macrophages is supposed to be involved in the apoptotic network on both sides: as a surface molecule of monocytes that can promote survival and antagonize apoptosis and as a recognition receptor of macrophages that enables or supports interaction with apoptotic cells. J. Leukoc. Biol. 65: 737–743; 1999.
The synthetic non-toxic drug 2,3-dimethyl-6(2-dimethylaminoethyl)-6H-indolo-(2,3-b)quinoxaline inhibits neutrophil production of reactive oxygen species
Authors: Harbecke Olle , Dahlgren Claes , Bergman Jan , Möller Lennart 
Published: January 2018

Abstract
The effects of the non-toxic drug 2,3-dimethyl-6(2-dimethylaminoethyl)-6H-indolo-(2,3-b)quinoxaline (B220) on the generation of reactive oxygen species from human neutrophils were investigated. The data show that B220 inhibits neutrophil release of reactive oxygen species, as well as intracellular generation of reactive oxygen species. The inhibition is not achieved through direct oxygen radical scavenger activity of B220, and the drug has no immediate effects on the activity of the assembled oxidase. Radical production and release were inhibited by all agonists tested [i.e. the protein kinase C-activating phorbol ester phobol myristate acetate; the receptor-specific agonist N-formyl-methionyl-leucyl-phenylalanine (fMLP); and serum-opsonized yeast particles] in the presence of B220. The drug also inhibits phagocytosis and fMLP-induced mobilization of granules. However, based on the fact that the effects of B220 on phagocytosis and granule mobilization are much less significant than its effect on radical production, we suggest that the signal(s) affected by B220 is (are) located mainly downstream of the point at which the signals are generated to promote oxidase activation and phagocytosis or granule secretion, respectively. J. Leukoc. Biol. 65: 771–777; 1999.
Identification of CD137 as a potent monocyte survival factor
Authors: Langstein Joachim , Schwarz Herbert 
Published: January 2018

Abstract
CD137 (ILA/4-1BB), a member of the tumor necrosis factor (TNF) receptor family, promotes adherence and prolongs survival of human peripheral monocytes. It induces a strong expression of macrophage colony-stimulating factor (M-CSF), an essential monocyte survival factor. Monocyte survival induced by CD137 is primarily mediated by M-CSF and to a lesser extent by granulocyte-macrophage colony-stimulating factor and IL-3. Survival and induction of M-CSF are mediated via reverse signaling through a CD137 ligand expressed constitutively by peripheral monocytes. J. Leukoc. Biol. 65: 829–833; 1999.
The role of chemokines in the regulation of dendritic cell trafficking
Authors: Sozzani Silvano , Allavena Paola , Vecchi Annunciata , Mantovan Alberto 
Published: January 2018

Abstract
The immunobiology of dendritic cells (DC) involves localization in tissues and trafficking via the lymph or blood to lymphoid organs. Appropriate assays representative of different steps of DC trafficking (e.g., reverse transmigration) provide the tools to dissect the migratory properties of these cells. Chemokines have emerged as important regulators of DC migration. DC are both the target and the source of chemokines. DC express receptors for and respond to a set of chemoattractants that overlap with, but are distinct from, those active on other leukocytes. Differential expression of the CCR6 receptor reveals heterogeneity among DC populations. Functional maturation is associated with loss of responsiveness to chemokines present at sites of inflammation and acquisition of a receptor repertoire that renders these cells responsive to signals that guide their localization in lymphoid organs. A better understanding of the molecular basis of DC trafficking may provide molecular and conceptual tools to direct and modulate DC traffic as a strategy to up-regulate and orient specific immunity. J. Leukoc. Biol. 66: 1–9; 1999.
Differential iron transport into phagosomes isolated from the RAW264.7 macrophage cell lines transfected with Nramp1Gly169 or Nramp1Asp169
Authors: Kuhn Donald E , Baker Beth D , Lafuse William P , Zwilling Bruce S 
Published: January 2018

Abstract
The transport of iron by RAW264.7 macrophage cell lines transfected with either Nramp1Gly169 (resistant) or Nramp1Asp169 (susceptible) alleles was assessed. We found no difference between resistant and susceptible cells in the rate of Fe import or export when Fe transport was measured in intact cells. In contrast, the rate of Fe import by latex-bead phagosomes isolated from resistant cells was more than double the rate by latex-bead phagosomes from susceptible cells. Similarly, phagosomes isolated from resistant cells that had been pre-labeled with 55Fe-citrate before phagocytosis contained up to four times as much Fe as the corresponding phagosomes from susceptible cells. Phagocytosis of Mycobacterium avium was accompanied by an increase in the production of hydroxyl radicals by Nramp1Gly169-transfected macrophages but not by macrophages transfected with the susceptible allele. These results are consistent with the hypothesis that Nramp1 functions to transport Fe into the bacterium-containing phagosome where it serves as a catalyst for the Haber-Weiss reaction, which accounts for the increased capacity of these cells to limit mycobacterial growth. J. Leukoc. Biol. 66: 113–119; 1999.
Urokinase plasminogen activator receptor (CD87) expression of tumor-associated macrophages in ductal carcinoma in situ, breast cancer, and resident macrophages of normal breast tissue
Authors: Hildenbrand Ralf , Wolf Georg , Böhme Beatrix , Bleyl Uwe , Steinborn Andrea 
Published: January 2018

Abstract
Macrophages concentrate urokinase-type plasminogen activator (uPA) at the cell surface by expressing urokinase receptors (uPAR) in order to focus the pericellular space plasminogen-dependent proteolysis important in matrix remodeling and cell movement. This study examines the uPAR levels of tumor-associated macrophages (TAM) of invasive breast carcinomas, of TAMs from ductal carcinoma in situ (DCIS) and of macrophages derived from normal (non-tumor) breast tissue. TAMs from invasive breast carcinomas (n = 30), from DCIS (n = 12), and macrophages from normal breast tissue (n = 30) were cultured and immunocytochemically phenotyped by using a panel of antibodies. Urokinase receptor levels were determined by Western blot analysis and in cell-free supernatants by enzyme-linked immunosorbent assay. Urokinase receptor cell surface fluorescence intensity was determined by FACS and by confocal laser scan microscopy. Urokinase-receptor mRNA was detected by in situ hybridization. TAMs of invasive breast carcinomas and of DCIS possess significantly elevated uPAR levels compared with macrophages derived from normal breast tissue. Conclusions: activated macrophages with elevated uPAR levels belong to inflammatory areas in close vicinity of infiltrating and non-infiltrating (DCIS) tumor cells. Blood monocytes that possess elevated uPAR-levels may be selectively recruited from the bloodstream to inflammatory sites close to carcinoma cells, and/or breast cancer and precursor lesions may induce elevated uPAR-levels in TAMs by paracrine interactions. J. Leukoc. Biol. 66: 40–49; 1999.
Mechanisms of ozone-induced inhibitory effect of bronchoalveolar lavage fluid on alveolar macrophage-mediated immunosuppressive activity in rats
Authors: Koike Eiko , Kobayashi Takahiro , Murakami Masataka , McWilliam Andrew S , Holt Patrick G 
Published: January 2018

Abstract
Resident alveolar macrophages (AM) play an important immunomodulatory role via suppression of lymphocyte proliferation, and nitric oxide (NO) plays a crucial role in this immunosuppression of AM. Our previous report suggested that during ozone (O3)-induced lung inflammation, bronchoalveolar lavage fluid (BALF) inhibited AM- mediated immunosuppression and concanavalin A (Con A)-induced proliferation of lymph node cells (LNC) [E. Koike et al. (1998) Toxicol. Sci. 41, 217–223]. In these studies, we investigated the mechanisms of the inhibition of BALF from O3-exposed rats (O3-BALF). We investigated whether BALF might affect (1) the interferon-γ (IFN-γ) production by Con A-stimulated LNC and IFN-γ-induced NO production by AM, and (2) the interleukin (IL)-2 production by Con A-stimulated LNC and IL-2-induced LNC proliferation. These results demonstrated that O3-BALF inhibited IFN-γ production by Con A-stimulated LNC, IFN-γ-induced NO production by AM, and IL-2-induced LNC proliferation. In addition, the major inhibitory factor against AM-mediated immunosuppression in O3-BALF may be a protein of greater than 10 kDa. J. Leukoc. Biol. 66: 75–82; 1999.
Immunobiology of DC in NOD mice
Authors: Morel Penelope A , Vasquez A Cecilia , Feili-Hariri Maryam 
Published: January 2018

Abstract
NOD mice spontaneously develop diabetes between 15 and 20 weeks of age, which is preceded by insulitis characterized by the infiltration of lymphocytes. Dendritic cells (DC) are among the first cells to infiltrate the islet and they have been implicated in the pathogenesis of the disease. Our work has been concerned with the detailed characterization of four distinct DC populations in NOD mice: two derived from bone marrow (BM) cells cultured in either granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4) or GM-CSF alone and two from the spleen of Flt3 ligand (Flt3L) -treated mice, isolated on the basis of CD8α expression. Phenotypic and functional differences between these DC subsets in NOD mice have been identified. In addition, we obtained a lower yield of NOD BM-derived DC and they expressed higher levels of cell-surface CD40 and IL-12 p40 mRNA than BM-derived DC from the diabetes-resistant strain, B10.BR. We have also investigated the ability of these DC populations to modulate the development and progression of diabetes in NOD mice. J. Leukoc. Biol. 66: 276–280; 1999.
Functional CD40 ligand is expressed on epidermal Langerhans cells
Authors: Salgado Claudio Guedes , Nakamura Koichiro , Sugaya Makoto , Tada Yayoi , Asahina Akihiko , Koyama Yoh-ichi , Irie Shinkichi , Tamaki Kunihiko 
Published: January 2018

Abstract
Epidermal Langerhans cells (LC) are bone-marrow-derived major histocompatibility complex (MHC) class II antigen-expressing antigen-presenting cells (APC) that comprise 1–3% of total epidermal cells (EC). LC express high levels of MHC class II antigen and augment costimulatory molecules such as B7-1, B7-2 during culture. In a previous report, using purified murine LC, we showed that freshly prepared LC (fLC) do not express CD40, whereas cLC express CD40. Tumor necrosis factor α (TNF-α) enhanced CD40 expression on LC during culture. We examined the expression of CD40L on LC and found that both fLC and cLC expressed mRNA for CD40L. FACS analysis revealed that cLC cultured for 36 h expressed CD40L but fLC did not. When we examined the cytoplasmic CD40L, however, both fLC and cLC expressed cytoplasmic CD40L. TNF-α, which up-regulated CD40 expression on LC during culture, did not modulate CD40L. Co-culture of purified LC with anti-CD40L markedly inhibited the up-regulation of B7-1 expression on LC and caused partial inhibition of B7-2 expression during culture. These results indicate that CD40L is expressed on cLC, and that CD40L on LC modulates the expression of costimulatory molecules such as B7-1 and B7-2 on LC. J. Leukoc. Biol. 66: 281–285; 1999.
Modulation of macrophage and B cell function by glycosaminoglycans
Authors: Wrenshall Lucile E , Stevens R Brian , Cerra Frank B , Platt Jeffrey L 
Published: January 2018

Abstract
There is increasing evidence that the behavior of antigen-presenting cells may be regulated, in part, by the surrounding microenvironment. Components of the microenvironment of solid tissues that might influence antigen-presenting cell functions include glycosaminoglycans. We previously showed that heparan sulfate glycosaminoglycans activate macrophages, leading to profound alterations in T cell responses. Here we demonstrate the functional changes that occur in murine antigen-presenting cells induced by heparan sulfate and other glycosaminoglycans, and postulate how these functional changes influence the nature of local immune responses. Heparan sulfate triggered up-regulation of ICAM-1 and I-A, caused the release by antigen-presenting cells of interleukin (IL)-1, IL-6, tumor necrosis factor, IL-12, transforming growth factor β, and prostaglandin E2 (PGE2), and (in macrophages) induced cytotoxic capability. Heparin induced IL-12 and interferon-γ production but did not promote the release of other cytokines. Chondroitin sulfate and dermatan sulfate, although not stimulating the production of cytokines or of PGE2, elicited the production by macrophages of nitric oxide. These findings support a model in which the glycosaminoglycan composition of a given tissue, which may be altered by inflammatory processes, helps to regulate the behavior of antigen-presenting cells, which in turn determines the characteristics of the immune response that ensues. J. Leukoc. Biol. 66: 391–400; 1999.
Short exposure of intestinal epithelial cells to TNF-α and histamine induces Mac-1-mediated neutrophil adhesion independent of protein synthesis
Authors: Miyata Ryukou , Iwabuchi Kazuhisa , Watanabe Sumio , Sato Nobuhiro , Nagaoka Isao 
Published: January 2018

Abstract
Neutrophils play an important role in intestinal inflammation by interacting with intestinal epithelial cells. In this study, we evaluated neutrophil adhesion to intestinal epithelial cells using intestinal epithelial cell line HT29 stimulated with tumor necrosis factor α (TNF-α) and histamine for a short time (30 min). The TNF-α and histamine stimulation markedly increased neutrophil adhesion. The increased adhesion was inhibited by anti-CD11b and anti-CD18 monoclonal antibodies (mAbs), but not by anti-CD11a and anti-CD54 (ICAM-1) mAbs. It is interesting that flow cytometric analysis revealed that ICAM-1 expression on HT29 cells was not changed by TNF-α and histamine stimulation. Moreover, the increased adhesion was inhibited by proteinase K treatment but not cycloheximide treatment of HT29 cells. Together these observations suggest that short exposure of HT29 cells to TNF-α and histamine induces CD11b/CD18 (Mac-1)-dependent but CD11a/CD18 (LFA-1)-independent neutrophil adhesion to intestinal epithelial cells, and ICAM-1 is not likely to be involved in the interactions. Furthermore, epithelial cell ligand(s) for neutrophils is likely protein molecule(s) that is expressed on the cell by stimulation independent protein synthesis. However, it is also possible that neutrophil activating factor(s), which stimulates neutrophils to bind with epithelial ligands via Mac-1, is expressed by epithelial cells during stimulation. J. Leukoc. Biol. 66: 437–446; 1999.
Localization of p21-activated kinase 1 (PAK1) to pseudopodia, membrane ruffles, and phagocytic cups in activated human neutrophils
Authors: Dharmawardhane Suranganie , Brownson Delia , Lennartz Michelle , Bokoch Gary M 
Published: January 2018

Abstract
Leukocyte chemoattractants are known to stimulate signaling pathways that involve Rho family GTPases. Direct evidence for the regulation of the leukocyte cytoskeleton by Rho GTPases and their effector targets is limited. The p21-activated kinases (PAKs) are specific targets of activated GTP-bound Rac and Cdc42, and have been proposed as regulators of chemoattractant-driven actin cytoskeletal changes in fibroblasts. PAK1 co-localizes with F-actin to cortical actin structures in stimulated fibroblasts, and activated PAK1 mutants induce membrane ruffling and polarized cytoskeletal rearrangements. We investigated whether PAK1 was associated with remodeling ofthe actin cytoskeleton in activated human neutrophils. We monitored the redistribution of PAK1 and F-actin into the actin cytoskeleton after stimulation of human neutrophils with the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP) or the particulate stimulus, opsonized zymosan (OZ). PAK1 exhibited a similar distribution as F-actin in fMLP-stimulated leukocytes, localizing in membrane ruffles and to lamellipodia at the leading edge of polarized cells. Addition of OZ induced phagocytic uptake of this particulate stimulus, and PAK1 re-localized to the F-actin-rich pseudopodia and phagocytic cups associated with this process. Once the OZ was internalized, there was little PAK1 localized around the ingested particles, suggesting that PAK1 may be regulating the cytoskeletal extensions and events required for engulfment of bacteria, but not the subsequent steps of internalization. Localization of PAK1 and F-actin in cytoskeletal structures was abolished by the actin polymerization inhibitor cytochalasin D and the phosphatidylinositol 3-kinase inhibitor wortmannin. Our data suggest that PAK1 may regulate a subset of cytoskeletal dynamics initiated by chemoattractant and phagocytic stimuli in human neutrophils. J. Leukoc. Biol. 66: 521–527; 1999.
The actions of bacterial DNA on murine macrophages
Authors: Sester David P , Stacey Katryn J , Sweet Matthew J , Beasley Shannon J , Cronau Stephen L , Hume David A 
Published: January 2018

Abstract
Murine macrophages are able to distinguish bacterial from mammalian DNA. The response is mimicked by single-stranded oligonucleotides containing unmethylated CG dinucleotides (“CpG” motifs) in specific sequence contexts. The dose-response curve for activation is influenced by variation in the sequence flanking the core CpG motif. CpG or bacterial DNA activates several signaling pathways in common with bacterial lipopolysaccharide (LPS), leading to induction of cytokine genes such as tumor necrosis factor a. Pretreatment with LPS causes desensitization to subsequent activation by CpG DNA. Both stimuli also cause cell cycle arrest in macrophages proliferating in response to the macrophage growth factor colony-stimulating factor-1 (CSF-1), but prevent apoptosis caused by growth factor removal. In part, cell cycle arrest by CpG DNA and LPS may be linked to rapid down-modulation of the CSF-1 receptor from the cell surface, a response that occurs in an all-or-nothing manner. The response of macrophages to CpG DNA has aspects in common with the DNA damage response in other cell types, which may provide clues to the underlying mechanism. J. Leukoc. Biol. 66: 542–548; 1999.