bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin signal transduction in myeloid leukocytes
Authors: Lowell Clifford A , Berton Giorgio 
Published: January 2018

Abstract
Integrin-mediated adhesion serves as a powerful costimulus for neutrophil activation. Clustering of integrins at the leukocyte membrane by interaction with surface-bound ligands (extracellular matrix proteins or endothelial cell counter-receptors) leads to a number of signaling events that culminate in actin cytoskeletal rearrangement and neutrophil functional responses such as migration, degranulation, and respiratory burst. Although the signaling reactions elicited by integrin ligation are complex and the relative contribution of each pathway to neutrophil function is unclear, a large body of evidence suggests that activation of tyrosine kinases is a very proximal event in these signaling cascades. This review summarizes the role of adhesion in activating neutrophil functional properties and the contribution of leukocyte tyrosine kinases to regulation of integrin signaling in myeloid cells. Significant advances in our understanding of leukocyte integrin signaling have been afforded by studies using knockout mice lacking members of the Src-family of tyrosine kinases normally expressed in myeloid cells. These studies have demonstrated that these kinases (Hck, Fgr, and Lyn) are not required for myeloid cell development or for many of the functional properties of myeloid cells but are critical in controlling integrin-mediated signaling events. Absence of these kinases results in impaired adhesion-dependent neutrophil activation both in vivo and in vitro. These studies suggest that leukocyte-specific tyrosine kinases may be good therapeutic targets for controlling myeloid cell-dependent inflammatory disease. J. Leukoc. Biol. 65: 313–320; 1999.
The SIV-infected rhesus monkey model for HIV-associated dementia and implications for neurological diseases
Authors: Rausch Dianne M , Murray Elisabeth A , Eiden Lee E 
Published: January 2018

Abstract
The neuropathogenesis of human immunodeficiency virus (HIV)-associated dementia has remained elusive, despite identification of HIV as the causal agent. Although a number of contributing factors have been identified, the series of events that culminate in motor and cognitive impairments after HIV infection of the central nervous system (CNS) are still not known. Rhesus monkeys infected with simian immunodeficiency virus (SIV) manifest immunosuppression and CNS disease that is pathologically [L. R. Sharer et al. (1991) J. Med. Primatol. 20, 211–217] and behaviorally [E. A. Murray et al. (1992) Science 255, 1246–1249] similar to humans. The SIV model of HIV-associated dementia (HAD) is widely recognized as a highly relevant model in which to investigate neuropathogenesis. With better understanding of neuropathogenesis comes the opportunity to interrupt progression and to design better treatments for HAD. This becomes increasingly important as patients live longer yet still harbor HIV-infected cells in the CNS. The use of the SIV model has allowed the identification of neurochemical markers of neuropathogenesis important not only for HAD, but also for other inflammatory neurological diseases. J. Leukoc. Biol. 65: 466–474; 1999.
Intracellular oxidant production and cytokine responses in lung macrophages: evaluation of fluorescent probes
Authors: Imrich Amy , Ning YaoYu , Kobzik Lester 
Published: January 2018

Abstract
The fluorescent probes dichlorofluorescin (DCFH), dihydrorhodamine (DHR), and hydro- ethidine (HE) allow convenient assay of alveolar macrophage (AM) oxidant responses to environmental particulates and pathogens. We sought to more precisely define the relationship of these measures of oxidant stress to production of pro-inflammatory cytokines. Normal AMs were challenged in vitro with a panel of soluble or particulate stimuli in the presence of DCFH, HE, or DHR. Flow cytometry measured cell-associated fluorescence and relative particle uptake. Tumor necrosis factor α and macrophage inflammatory protein 2 expression were quantitated in the same experiments. We observed variable and complex correlations between intracellular oxidant production as reported by these probes and subsequent cytokine response, including examples of striking discordance (e.g., lipopolysaccharide induced large cytokine responses with minimal probe oxidation, whereas fly ash particles caused marked oxidation of DCFH but trivial TNF release; TiO2 caused oxidation of DHR and HE, but not DCFH, and also did not increase cytokine production). Although fluorescent probes offer many advantages in analysis of intracellular oxidant responses, the data indicate that they cannot be used reliably as quantitative predictors of AM cytokine responses to environmental particulates or other stimuli. J. Leukoc. Biol. 65: 499–507; 1999.
Chemokine immunobiology in HIV-1 pathogenesis
Authors: Leen Benhur , Montaner Luis J 
Published: January 2018

Abstract
The discovery of HIV-1-suppressive chemokines and the subsequent discovery of their cognate receptors as coreceptors for HIV-1 entry herald a paradigmatic shift in the study of HIV-1 pathogenesis. The presence of polymorphisms in chemokine receptor and chemokine genes associated with altered progression and susceptibility to the HIV-1 disease further underscores the potential importance that chemokines and their cognate receptors play in HIV-1 pathogenesis. It has become increasingly apparent that the immune system maintains a delicate balance between the positive and negative regulators that govern the chemokine and cytokine networks. Here we review the most recent developments in chemokine biology and relate how research into their structure, regulation, and the mechanism of their actions can shed light on the immunopathogenesis of HIV-1 disease. J. Leukoc. Biol. 65: 552–565; 1999.
Dramatic decrease of circulating levels of monocyte chemoattractant protein-1 in Kawasaki disease after gamma globulin treatment
Authors: Terai Masaru , Jibiki Toshiaki , Harada Akihisa , Terashima Yuya , Yasukawa Kumi , Tateno Shigeru , Hamada Hiromichi , Oana Shinji , Niimi Hiroo , Matsushima Kouji 
Published: January 2018

Abstract
Kawasaki disease (KD) is a systemic vasculitis preferentially affecting coronary arteries. Extensive monocytes/macrophages infiltrate in the vascular lesions, implying the involvement of a chemotactic cytokine in their recruitment. We investigated the role of monocyte chemoattractant protein-1 (MCP-1, also termed monocyte chemotactic and activating factor) in KD. In the immunohistochemical studies using the cardiac tissues of patients with fatal KD, MCP-1 but not interleukin (IL) -8 or macrophage inflammatory protein-1α was localized at the extracellular matrix associated with mononuclear cellular infiltration. The sites of MCP-1 expression correlated with the distribution of the acute inflammation, including early coronary vasculitis. In prospectively studied patients with KD, circulating levels of MCP-1, IL-8, tumor necrosis factor a (TNF-α), and IL-1α were elevated in 73, 77, 57, and 0% of samples before gamma globulin (GG) treatment (400 mg/kg × 5 days = total 2 g/kg), respectively, compared with respective control values. GG treatment correlated with a rapid decrease in the circulating levels of MCP-1 (P = 0.001) but not IL-8 (P = 0.19) or TNF-α (P = 0.33). In the sensitive Western blotting, MCP-1 bound to GG. Furthermore, GG inhibited the MCP-1-induced Ca2+ influx in a human monocytic cell line in vitro. These findings suggest a role of MCP-1 in KD, and indicate that GG treatment may block MCP-1 activity, thus alleviating KD vasculitis. J. Leukoc. Biol. 65: 566–572; 1999.
Demonstration of iNOS-mRNA and iNOS in human monocytes stimulated with cancer cells in vitro
Authors: Siedlar Maciej , Mytar Bozenna , Krzeszowiak Agnieszka , Baran Jaroslaw , Hyszko Mariola , Ruggiero Irena , Wieckiewicz Jerzy , Stachura Jerzy , Zembala Marek 
Published: January 2018

Abstract
Synthesis and localization of inducible nitric oxide synthase mRNA (iNOS-mRNA) and iNOS protein in the cultures of human monocytes (Mφ) and colon carcinoma cell line (DeTa) that resulted in nitric oxide (NO) synthesis has been studied. The iNOS-mRNA was observed around the sixth hour of culture and peaked at the twelfth hour. The iNOS-mRNA, as determined by the in situ hybridization and iNOS protein, as detected by staining with specific anti-iNOS monoclonal antibodies, were observed preferentially in the cytoplasm of some Mφ, but not in cancer cells. Mφ cultured alone did not show detectable iNOS-mRNA expression and iNOS protein. Mφ sorted out from tumor cells after 8hof co-culture expressed iNOS protein and iNOS-mRNA, which were not detected in Mφ without previous contact with cancer cells. Prevention of NO synthesis by (L-N5-1-iminoethyl)-ornithine (L-NIO) partly inhibited Mφ cytotoxic activity against DeTa (NO-inducing cancer cell line) but not against the human pancreatic cancer (HPC-4) cell line that does not induce NO production in Mφ. This suggests that Mφ cytotoxic activity, at least in some cases, may be NO dependent. These observations provide further evidence that Mφ can be directly stimulated by cancer cells for de novo production of NO and suggest that iNOS occurring in the tumor-infiltrating macrophages may arise as a result of their interactions with tumor cells. However, because only some tumor cells are able to induce NO production in a small proportion of Mφ, its role in the anti-tumor response of the host is probably limited. J. Leukoc. Biol. 65: 597–604; 1999.
Interaction with vesicular stomatitis virus-infected BALB/c3T3 cells inhibits the synthesis of nitric oxide in activated murine bone marrow culture-derived macrophages
Authors: Crowder Chun W , Murphy William J , Russell Stephen W , LeBlanc Paul A 
Published: January 2018

Abstract
Bone marrow-culture-derived macrophages activated with interferon-γ and lipopolysaccharide produced less nitric oxide (NO) when cultured with vesicular stomatitis virus (VSV)-infected BALB/c3T3 (3T3-VSV) than macrophages activated in an identical manner and cultured alone, with uninfected BALB/c3T3 (3T3), or with P815. However, all four groups of macrophages produced nearly the same amount of interleukin-6 (IL-6). Addition of VSV to activated macrophages did not change the amount of NO produced. The amount of NO generated by two non-macrophage sources of NO was not affected by the presence of either P815 or 3T3-VSV. Reverse transcriptase-polymerase chain reaction showed a decrease in the amount of inducible nitric oxide synthase (iNOS) but not IL-6 mRNA from macrophages cocultured with 3T3-VSV compared with macrophages cocultured with P815. The reduction in iNOS mRNA was confirmed by ribonuclease protection assay. When RAW 264.7 transfected with an iNOS regulatory construct were activated and incubated with 3T3-VSV there was a decrease in the expression of the reporter luciferase gene and NO production but not IL-6 production compared with cells incubated with either medium alone or with P815. J. Leukoc. Biol. 65: 605–613; 1999.
Hyperglycemia in vitro attenuates insulin-stimulated chemokinesis in normal human neutrophils. Role of protein kinase C activation
Authors: Oldenborg Per-Arne , Sehlin Janove 
Published: January 2018

Abstract
This study was performed to test whether the inhibitory effect of elevated D-glucose concentrations on insulin-stimulated chemokinesis in normal human neutrophils is mediated by increase in protein kinase C (PKC) activity. Activation of PKC with phorbol 12-myristate 13-acetate (PMA) at 0–100 nM dose-dependently inhibited neutrophil random locomotion in the absence of insulin. Suboptimal concentrations of PMA (0.1–0.5 nM) inhibited the chemokinetic effect of 160 μU/mL insulin in a dose-dependent way. The specific PKC inhibitor bisindolylmaleimide (GF 109203x) did not affect the insulin-stimulated chemokinesis at 5 mM glucose but restored the chemokinetic effect of insulin at 15 mM glucose. These results therefore suggest that glucose-induced PKC activation may mediate the inhibitory effects of high glucose levels on insulin-stimulated chemokinesis in normal human neutrophils. J. Leukoc. Biol. 65: 635–640; 1999.
Enhancement of leukocyte response to lipopolysaccharide by secretory group IIA phospholipase A2
Authors: Cai Tian-Quan , Thieblemont Nathalie , Wong Birming , Thieringer Rolf , Kennedy Brian P , Wright Samuel D 
Published: January 2018

Abstract
Secretory nonpancreatic group IIA Phospholipase A2 (sPLA2), a lipolytic enzyme found in plasma, is thought to play an important role in inflammation. In patients with sepsis, a strong positive correlation is observed between the plasma level of sPLA2 and poor clinical outcome in sepsis. We have thus asked whether sPLA2 could play a role in enabling responses of cells to bacterial lipopolysaccharide (LPS), a key contributor to sepsis. In the presence of sPLA2, cellular responses to LPS were significantly increased. This was demonstrated in assays of LPS-stimulated interleukin-6 (IL-6) production in whole blood and binding of freshly isolated human polymorphonuclear neutrophils (PMN) to fibrinogen-coated surfaces. We further found that sPLA2 enhanced binding of labeled LPS to PMN, and that the sPLA2-mediated cell responses to LPS were all blocked by monoclonal antibodies directed against membrane CD14. Two properties of sPLA2 may contribute to its activity to mediate responses to LPS. sPLA2 appears to bind LPS because pre-exposure of sPLA2 to LPS led to a dose-dependent increase in its ability to hydrolyze phospholid substrate, and incubation of sPLA2 with BODIPY-LPS micelles resulted in enhanced fluorescence, presumably from the disaggregation of the LPS aggregates. Additional studies demonstrated that the esterolytic function of sPLA2 is also needed both for the disaggregation of LPS and CD14-dependent cell stimulation. The precise mechanisms by which LPS-binding and esterolytic activity contribute to sPLA2 activity are not clear but our data strongly suggest that these activities result in interaction of LPS with CD14 and subsequent cell activation. J. Leukoc. Biol. 65: 750–756; 1999.
An autologous self-antigen differentially regulates expression of I-A glycoproteins and B7 costimulatory molecules on CD4− CD8− T helper cells
Authors: Walker Mindi R , White Gregory A , Nardella John P , Mannie Mark D 
Published: January 2018

Abstract
During inflammation, T helper cells transiently express class II major histocompatibility complex (MHC) glycoproteins and present antigens to other T cells. To assess involvement of self-antigens in the generation of T cell antigen-presenting cell (T-APC) activity, rat (R) myelin basic protein (MBP) was used to stimulate a rat CD4−CD8− T cell clone. RMBP induced T cell surface expression of class II MHC glycoproteins and T-APC activity, although RMBP did not elicit interleukin (IL-2) production or proliferation. When added to culture with the strong agonist guinea pig (GP) MBP, RMBP acted as a partial antagonist and inhibited responses of IL-2 production, proliferation, and T cell expression of B7.1. RMBP did not, however, efficiently antagonize GPMBP-induced I-A expression on T cells. These findings indicate that the self-antigen RMBP specifically induces accumulation of I-A/peptide complexes at signaling thresholds that inhibit pathogenic autoimmune responses. Overall, this study suggests a role for self-antigens in the generation of B7-deficient T-APC activity as a mechanism of tolerance in experimental autoimmune encephalomyelitis. J. Leukoc. Biol. 66: 120–126; 1999.
Modulation of CXCR4 expression and SDF-1α functional activity during differentiation of human monocytes and macrophages
Authors: Gupta Shalley K , Pillarisetti Kodandaram , Lysko Paul G 
Published: January 2018

Abstract
Chemoattraction of monocytes by the CXC chemokine stromal cell-derived factor-1α (SDF-1α) and its receptor CXCR4 may be involved in vascular diseases like atherosclerosis. We studied the regulation of CXCR4 transcription and SDF-1-induced functional responses in human monocytes during their differentiation in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), oxidized low-density lipoprotein (Ox-LDL), and unmodified LDL. Our results reveal that the rapid decline of SDF-1-mediated [Ca2+]i influx after monocyte isolation is followed by a gradual functional restoration and a concomitant re-expression of CXCR4 mRNA over time. A further three- to fourfold induction of CXCR4 mRNA occurred in macrophage-derived foam cells on treatment with Ox-LDL. HL-60 cells induced with phorbol myristate acetate (PMA) showed a rapid fourfold stimulation of CXCR4 mRNA within 1 h, declining to barely detectable levels at 3 h, with eventual restoration over time, mirroring the expression pattern in monocytes. Surface expression of CXCR4 is maintained in HL-60 cells during PMA-induced differentiation, as demonstrated by flow cytometry. GM-CSF had no effect on CXCR4 mRNA in HL-60 cells and does not cause its down-regulation in human macrophages. J. Leukoc. Biol. 66: 135–143; 1999.
The initiation of the neutrophil chemotactic response in filters
Authors: Ebrahimzadeh P R , Braide M 
Published: January 2018

Abstract
The fluid gradient chamber was used to study the migration of human neutrophils in preformed gradients of N-formyl-methionyl-leucyl-phenylalanine. After 60 min, the chemotactic gradient was replaced by a new one of identical steepness but opposite direction. In a control group of experiments, the first gradient was retained. Migration was assessed from cell distributions in filter sandwiches after 30, 60, and 90 min. Filters obtained after 5, 15, and 30 min of migration were stained with fluorescent phalloidin for microscopic evaluations of cell polarity. At 30 min most cells had polarized in vertical directions and invaded the filters. The distance of chemotactic migration was similar during the second and the third 30-min periods (although the direction of migration was reversed in the new gradient) and significantly greater than during the first 30 min. In conclusion, the initial slow response to the chemotactic gradient represents an adaptation of the cells that later respond promptly to changes in gradient direction. J. Leukoc. Biol. 66: 90–94; 1999.
Infusion of donor leukocytes to induce tolerance in organ allograft recipients
Authors: Salgar S K , Shapiro R , Dodson F , Corry R , McCurry K , Zeevi A , Pham S , Abu-Elmagd K , Reyes J , Jordan M , Keenan R , Griffith B , Sesky T , Ostrowski L , Starzl T E , Fung J J , Rao A S 
Published: January 2018

Abstract
To further enhance chimerism, 229 primary allograft recipients have received perioperative intravenous infusion of a single dose of 3 to 6 × 108 unmodified donor bone marrow (BM) cells/kg body weight. In addition, 42 patients have been accrued in a concurrent protocol involving multiple (up to three) sequential perioperative infusions of 2 × 108 BM cells/kg/day from day 0–2 posttransplantation (PTx). Organ recipients (n = 133) for whom BM was not available were monitored as controls. The infusion of BM was safe and except for 50 (18%), all study patients have optimal graft function. Of the control patients, allografts in 30 (23%) have been lost during the course of follow-up. The cumulative risk of acute cellular rejection (ACR) was statistically lower in the study patients compared with that of controls. It is interesting that, 62% of BM-augmented heart recipients were free of ACR (Grade ≥ 3A) in the first 6 months PTx compared to controls. The incidence of obliterative bronchiolitis was also statistically lower in study lung recipients (3.8%) compared with the contemporaneously acquired controls (31%). The levels of donor cell chimerism were at least a log higher in the peripheral blood of majority of the study patients compared with that of controls. The incidence of donor-specific hyporeactivity, as determined by one-way mixed leukocyte reaction, was also higher in those BM-augmented liver, kidney, and lung recipients that could be evaluated compared to controls. J. Leukoc. Biol. 66: 310–314; 1999.
Ubiquicidin, a novel murine microbicidal protein present in the cytosolic fraction of macrophages
Authors: Hiemstra Pieter S , van den Barselaar Maria T , Roest Mark , Nibbering Peter H , van Furth Ralph 
Published: January 2018

Abstract
Previously we have identified and characterized three murine microbicidal proteins purified from the granule fraction of cells from the murine macrophage cell line RAW264.7. During these studies evidence was obtained for the presence of an additional antimicrobial protein in the cytosolic fraction of RAW264.7 cells that had been activated with interferon-γ (IFN-γ). In this study we have purified this protein, designated ubiquicidin, to apparent homogeneity and demonstrated that it is a cationic, small (Mr 6654) protein. Ubiquicidin displayed marked antimicrobial activity against Listeria monocytogenes and Salmonella typhimurium. Using a gel overlay procedure evidence was obtained that the protein also displays activity against Escherichia coli, Staphylococcus aureus, and an avirulent strain of Yersinia enterocolitica. Amino-terminal amino acid sequencing and mass spectrometry analysis of purified ubiquicidin indicated that it is most likely identical to the ribosomal protein S30. This protein is produced by posttranslational processing of the Fau protein, a 133-amino-acid fusion protein consisting of S30 linked to an unusual peptide with significant homology to ubiquitin. The fau gene has been reported to be expressed in a variety of tissues in humans and various animal species. The presence of ubiquicidin in the cytosol of macrophages may serve to restrict the intracellular growth of microorganisms. In addition, because macrophage disintegration will likely lead to release of ubiquicidin into the extracellular environment, it may contribute to host defense after macrophage death. J. Leukoc. Biol. 66: 423–428; 1999.
The generation of human dendritic and NK cells from hemopoietic progenitors induced by interleukin-15
Authors: Bykovskaia Svetlana N , Buffo Mary , Zhang Haifan , Bunker Mark , Levitt Mark L , Agha Mounzer , Marks Stanley , Evans Carol , Ellis Peter , Shurin Michael R , Shogan Jeffrey 
Published: January 2018

Abstract
Interleukin-15 (IL-15) is a pleiotropic cytokine that induces the generation and differentiation of lymphoid cells and shares many biological activities with IL-2. We have shown here the development of dendritic cells (DC) from human CD34+ hemopoietic precursor cells cultured for 2–4 weeks with IL-15 alone. DC generated with IL-15 have typical morphological, immunocytochemical, phenotypic, and functional characteristics of mature DC. Dual flow cytometry analysis performed weekly demonstrated increasing co-expression of CD1a or CD83 with HLA-DR, CD80, CD86, IL-2R α, β, and γ. Two populations of cells were distinguished among CD34+ progeny. Small and medium-size cells were mainly natural killer (NK) cells (72.6–85.2% CD56+) and low numbers of DC (9.1–21.3% CD1a+). Large cells were mostly DC (75.4–95.4% CD1a+). Isolated CD34+ cells did not express IL-2R subunits but after 2–3 days in culture with IL-15, they were found to express IL-2Rγ. Induced expression of IL-2Rγ on CD34+ cells may explain the primary mechanism of IL-15-regulated differentiation of hemopoietic precursor cells. Thus, our data suggest that IL-15 stimulates CD34+ cells to differentiate into NK and DC and may represent a new growth and survival factor for lymphoid DC. J. Leukoc. Biol. 66: 659–666; 1999.