bluuebunny/crossref_metadata_2025_split huggingface dataset:
The α4β1 integrin can mediate leukocyte adhesion to casein and denatured protein substrates
Authors: Davis George E , Thomas J Scott , Madden Steven 
Published: January 2018

Abstract
An understanding of the binding specificity of leukocyte integrins is important to determine the range of ligands that interact with these receptors during inflammatory processes. In this study we show that the α4β1 integrin can interact with casein and denatured albumin and promote leukocyte adhesion through these interactions. This was demonstrated with the use of blocking antibodies directed to α4β1 and peptide adhesion competitors containing the α4β1 binding tripeptide, Leu-Asp-Val (LDV). Consistent with this data, the adhesion is completely divalent cation-dependent and is stimulated by known activators of leukocyte integrin function, namely phorbol ester and the β1 integrin activating antibody, 8A2. It is interesting to note that neither bovine α-casein or human albumin contain an LDV site (present in the CS-1 site of alternatively spliced fibronectin) or an IDS site (present in VCAM-1) yet they promote adhesion through this integrin. Furthermore, α4β1 directly binds to Sepharose columns containing casein, casein fragments, or denatured albumin but does not bind columns containing native albumin. These data suggest that the binding specificity for the α4β1 integrin is considerably broader than previously realized. This work has implications for how subsets of leukocytes may interact with damaged proteins during tissue injury and inflammation.
A cytosolic calcium transient is not necessary for degranulation or oxidative burst in immune complex-stimulated neutrophils
Authors: Seetoo Kurt F , Schonhorn Jeremy E , Gewirtz Andrew T , Zhou Ming Jie , McMenamin Mary E , Delva Luisette , Simons Elizabeth R 
Published: January 2018

Abstract
Receptor-mediated activation of neutrophils (PMN) initiates possibly interdependent events, including a rapid transient increase in [Ca2+]i, implicated as a second messenger. To investigate whether this transient is required for eventual degranulation, PMN were incubated with an intracellular Ca2+ chelator (BAPTA), then exposed to chemotactic peptide [N-formyl-methionyl-leucyl-phenylalanine (fMLP)] with or without cytochalasin B (CB) or to high-valency immune complexes (HIC); δ[Ca2+]i, δpHi, oxidative burst, and elastase release were then evaluated (plus or minus EGTA 15 s before stimulation) after 2 and 15 min incubation in 0.9 mM Ca2+. With either fMLP plus CB or HIC stimulation, BAPTA-treated cells were unable to achieve a Ca2+ transient with a 2-min incubation, whereas a 15-min incubation allowed the BAPTA-treated cells to recover a portion of the δ[Ca2+]i. Even though BAPTA-treated cells were unable to mount a δ[Ca2+]i at 2 min, HIC-stimulated BAPTA-treated cells were able to elicit an oxidative burst (33% of control) and degranulation (67% of control). Therefore, we conclude that δ[Ca2+]i modulates but is not required for oxidative burst or degranulation.
Effects of inhibitors of inflammatory mediators and cytokines on eosinophil and neutrophil accumulation induced by Mycobacterium bovis bacillus Calmette-Guérinin mouse pleurisy
Authors: Menezes-de-Lima-Júnior Octávio , Werneck-Barroso Eduardo , Cordeiro Renato S B , das Graças Maria , Henriques M O 
Published: January 2018

Abstract
In this work we characterize the Mycobacterium bovis bacillus Calmette-Guérin(BCC) -induced pleurisy and investigate the role of chemical mediators and cytokines in BCG-induced granulocyte accumulation at 24 h. Intrathoracic injection of BCG in C57B1/6 mice induces a biphasic inflammatory reaction with intense leukocyte accumulation at 24 h and 15 days. Neutrophils were observed in the pleural cavity at 4-24 h, mononuclear cells and eosinophils after 24 h. A new wave of mononuclear cells and neutrophils were observed after 15 days. Pretreatments with dexamethasone, BW 755C, BW A4C, WEB 2170, L-NAME, and monoclonal antibody (mAb) anti-interleukin-5 (IL-5; TRFK-5) had inhibited the eosinophil accumulation. On the other hand, only the pretreatments with dexamethasone, L-NAME, or mAb antitumor necrosis factor a (TNF-α; MP6-XT3) had inhibited the neutrophil influx. These results suggest the involvement of leukotrienes, platelet-activating factor, nitric oxide, and IL-5 in the eosinophil accumulation, and a role for nitric oxide and TNF-α in the neutrophil influx induced by BCG.
Glutathione peroxidase activity and mRNA expression in eosinophils and neutrophils of asthmatic and non-asthmatic subjects
Authors: Misso Neil L A , Peroni Darryl J , Watkins D Neil , Stewart Geoffrey A , Thompson Philip J 
Published: January 2018

Abstract
Asthma has been reported to be associated with a reduction in the activity of glutathione peroxidase (GSH-Px), an important antioxidant enzyme. However, the expression of GSH-Px enzyme activity has not previously been investigated in human eosinophils, which are important inflammatory cells involved in asthma. Reverse transcriptase-polymerase chain reaction and Southern blotting demonstrated that eosinophils express GSH-Px mRNA and the relative expression of GSH-Px was greater in eosinophils than in neutrophils for both asthmatic and non-asthmatic subjects. The presence of GSH-Px protein in eosinophil and neutrophil lysates was confirmed by size exclusion chromatography and by Western blotting. GSH-Px enzyme activity as measured by a spectrophotometric assay was greater in eosinophil (48.4 ± 1.6 μmol NADPH oxidized · min–1 · g–1 protein) than in neutrophil lysates (18.1 ± 0.4, n = 24, P &lt; 0.0001). GSH-Px activities of eosinophils and neutrophils from asthmatic subjects did not differ from those of non-asthmatic subjects. Eosinophil GSH-Px activity was correlated with peripheral blood eosinophil count only in asthmatic subjects (rs = 0.59, n = 12, P = 0.04). Increased GSH-Px expression in eosinophils compared with neutrophils of asthmatic patients may provide antioxidant protection against the greater amounts of reactive oxygen species generated by these cells and may enhance the survival of eosinophils at sites of inflammation in asthma.
Modulation of cell adhesion molecules on human endothelial cells by eosinophil-derived mediators
Authors: Molet S , Gosset P , Vanhee D , Tillie-Leblond I , Wallaert B , Capron M , Tonnel A-B 
Published: January 2018

Abstract
Mechanisms that allow a selective eosinophil emigration in different eosinophilic lung diseases remain poorly understood. In this study, we tested the hypothesis that eosinophils might participate in their own recruitment, particularly through adhesion molecule expression on human endothelial cells (EC). Blood eosinophils from donors with blood eosinophilia were purified and maintained in culture medium for 1 and 18 h. The expression of ICAM-1, E-selectin, and VCAM-1 on human umbilical vein endothelial cells (HUVEC) was evaluated by ELISA and flow cytometry analysis after addition of eosinophil supernatants. Eosinophil supernatants collected after 1 h induced a weak increase of CAM expression on HUVEC. In contrast, supernatants from eosinophils cultured for 18 h considerably amplified ICAM-1, E-selectin, and VCAM-1 expression on the surface of EC. These levels of CAM expression (in optical density determined by ELISA) were about two- or threefold more important than those obtained with eosinophil supernatants collected after a 1-h culture. The characterization of the implicated molecules showed that anti-IL-1β antibodies significantly inhibited ICAM-1, E-selectin, and VCAM-1 expression, whereas anti-TNF-α antibodies only induced a moderate inhibition. Our data support the hypothesis that eosinophils, through the release of at least IL-1β and TNF-α, might participate in the amplification of the inflammatory reaction by activating the vascular endothelium.
HIV-1 induces human monocyte-derived macrophages to produce C3 and to fix C3 on their surface
Authors: Bajtay Zsuzsa , Kacani Laco , Erdei Anna , Dierich Manfred P 
Published: January 2018

Abstract
Complement components, particularly C3, are known to be involved in the pathogenesis of AIDS and macrophages may serve as a source of C3 at sites of infection. We investigated whether the interaction between HIV-1 and monocytes has any effect on C3 production by the cells. Monocytes isolated from the blood of healthy volunteers were incubated with monocytotropic and T lymphocytotropic HIV-1 strains or with recombinant gp160 and cultured in serum-free medium up to 7 days. Supernatants were tested for secreted C3 by enzyme-linked immunosorbent assay. Our data show that monocytes cultured with either the monocytotropic or the T lymphocytotropic HIV-1 strains produce C3 in large amounts. The effect of both viruses is dose dependent and the amount of C3 induced by HIV was up to 20-fold higher than in the control samples. C3 production was also enhanced by gp160, the envelope protein of the virus. Secretion of IL-6 by the cells was also measured and found to be elevated up to threefold as a consequence of the interaction with the virus. HIV-1-activated monocyte-derived macrophages acquired the capacity to cleave exogenous C3 and to fix generated C3 fragments on their cell membrane.
Urinary levels of chemokines (MCAF/MCP-1, IL-8) reflect distinct disease activities and phases of human IgA nephropathy
Authors: Yokoyama Hitoshi , Wada Takashi , Furuichi Kengo , Segawa Chikako , Shimizu Miho , Kobayashi Ken-ichi , Su Shao-bo , Mukaida Naofumi , Matsushima Kouji 
Published: January 2018

Abstract
Leukocytes have been implicated to be involved in the pathogenesis of IgA nephropathy (IgAN). To clarify the precise molecular mechanism of recruitment and activation of leukocytes in the subgroups of IgAN, latent, acute, and chronic types, we studied monocyte chemotactic and activating factor (MCAF/MCP-1) and interleukin (IL)-8 in urines and renal expression of these cytokines. Urinary MCAF levels were significantly higher in chronic type, and were correlated with pathological progressive factors such as mesangial proliferation and interstitial cellular infiltration associated with CD68-positive macrophage. On the other hand, urinary IL-8 elevated only in acute type and were correlated with glomerular endocapillary proliferation and the degree of hematuria. In immunohistochemical study, IL-8 was mainly observed in glomeruli, otherwise MCAF in vascular endothelial cells, tubular epithelial cells, and infiltrated mononuclear cells in the interstitial lesions. These observations demonstrated that MCAF and IL-8 were differentially expressed in kidneys with IgAN, and their subtypes, and suggest that chemokines may be involved in the pathogenesis of IgAN at distinct phases or pathological lesions, possibly through the recruitment and activation of a distinct type of leukocyte.
Signal transduction by immunoglobulin Fc receptors
Authors: Sánchez-Mejorada Gabriela , Rosales Carlos 
Published: January 2018

Abstract
Receptors for the Fc portion of immunoglobulin molecules (FcR) present on leukocyte cell membranes mediate a large number of cellular responses that are very important in host defense. Cross-linking of FcR by immune complexes leads to functions such as phagocytosis, cell cytotoxicity, production and secretion of inflammatory mediators, and modulation of the immune response. Molecular characterization of FcRs indicates the existence of several types of these receptors, which seem to be redundant in their cell distribution and function. There is a great deal of interest in understanding how these various receptors signal the cell to respond in different ways during inflammation and the immune response. Previous studies indicate that FcR signaling shares elements with the T and B cell antigen receptors. Signaling is initiated in all of them by activation of tyrosine kinases of the Src and ZAP-70 families. Subsequent events, which vary depending on the cell type and receptor involved, include activation of other enzymes such as phospholipase Cγ1, phosphatidylinositol-3-kinase, and mitogen-activated protein kinase. Several recent lines of research, including studies of phagocytosis by FcR-transfected cells, antibody-dependent cytotoxicity by natural killer cells, mast cell degranulation, and FcR-deficient mice, have given us new insights on the signal transduction pathways activated by FcRs. This review describes the advances in these areas and presents a general model for FcR-mediated signaling.
Arterial and venular endothelial cell costimulation of cytokine secretion by human T cell clones
Authors: Johnson David R , Hauser Ingeborg A , Voll Reinhard E , Emmrich Frank 
Published: January 2018

Abstract
Vascular endothelial cell (EC) costimulation of cytokine secretion by T lymphocytes may be important in inflammation and allograft rejection. Venous and arterial iliac endothelial cells (VIEC, AIEC) both costimulate interleukin-2 (IL-2) production by peripheral blood lymphocytes (PBL) or T cell clones stimulated with phytohemagglutinin (PHA). Interferon-γ (IFN-γ) production is costimulated in a subset of clones but IL-4 is not. Surprisingly, two T cell clones were reciprocally better costimulated by VIEC or AIEC. EC activation by pretreatment with tumor necrosis factor α (TNF-α) does not increase T cell costimulation despite large increases in EC cell adhesion molecule expression. Neither VIEC nor AIEC express CTLA4-binding molecules and costimulation is blocked by cyclosporin A, suggesting that CD28 is not involved in EC costimulation of T cells. These data suggest that adult vascular EC costimulate production of IL-2 and IFN-γ but not IL-4 by mature T cells, that EC costimulation is not increased in inflamed tissues, and that different EC optimally costimulate particular T cells. These findings have implications for the nature of the costimulatory signal(s) provided by EC and may be important in understanding vasculitis or atherosclerosis.
Potential involvement of IL-8 in the pathogenesis of human cytomegalovirus infection
Authors: Murayama Tsugiya , Mukaida Naofumi , Khabar Khalid S A , Matsushima Kouji 
Published: January 2018

Abstract
The observations that several types of viruses induced interleukin (IL)-8 production prompted us to investigate the interrelationship between IL-8 and cytomegalovirus (CMV) infection. CMV infection caused IL-8 production in a human monocytic cell line, THP-1, in dose- and time-dependent manners. Moreover, CMV induced IL-8 gene expression by concurrently activating transcription factors, NF-κB and AP-1. Furthermore, CMV infection of human fibroblast cell lines increased gene expression of a specific receptor for IL-8, CXCR1. IL-8 in turn enhanced CMV replication in a human embryonic fibroblast, MRC-5, in dose- and time-dependent manners. Augmented replication eventually culminated in the increased production of infectious CMV virions. Moreover, IL-8 can attenuate the antiviral activity of interferon (IFN), particularly that of α-type against picornaviruses such as encephalomyocarditis virus and poliovirus. The inhibitory effects were associated with reduced 2′,5′-A oligoadenylate synthetase activity. These results would imply that CMV can induce IL-8, which can augment CMV replication directly and indirectly by counteracting antiviral activity of IFN. J. Leukoc. Biol. 64: 62–67; 1998.
Altered levels of urokinase on monocytes and in serum of children with AIDS; effects on lymphocyte activation and surface marker expression
Authors: Murali Rama , Wolfe Joshua H , Erber Rebecca , Chice Seto M , Murali M R , Durkin Helen G , Zach Petr , Auci Dominick L 
Published: January 2018

Abstract
Urokinase (UK) type plasminogen activator is a serine protease produced by activated human monocytes. Despite the well-documented roles played by UK in cell-mediated immunity in healthy humans, the roles played by UK in the derangements of cell-mediated immune responses observed in HIV disease remain largely undefined. In these studies the numbers of peripheral blood lymphocytes and monocytes bearing surface UK (UK+) as well as serum levels of UK (flow microfluorimetry and ELISA, respectively) were determined in children with AIDS and in healthy HIV-negative children. The effects of exogenous UK on lymphocyte activation (cell cycle analysis using living cells) and surface marker (CD3, CD4, CD8, and CD19) expression (flow microfluorimetry using fixed cells) were also studied. Data are expressed as percent total cells. Numbers of UK+ lymphocytes in children with AIDS were similar to those observed in healthy children. In contrast, numbers of UK+ peripheral blood monocytes were dramatically decreased (&gt;70%) in the children with AIDS. However, serum levels of UK were increased (nearly threefold) in these children. When lymphocytes from these children were cultured with soluble UK, numbers of cells in S phase of cell cycle appeared suppressed. Incubation of fixed lymphocytes from either a child with AIDS or from a healthy child with exogenous UK appeared to increase numbers of cells expressing CD3. Incubation with UK had no effect on expression of any other surface marker (CD4, CD8, or CD19) using cells from the child with AIDS. In contrast, incubation with UK appeared to decrease (fivefold) numbers of cells expressing CD19 and increase numbers of cells expressing CD4 and CD8 only when fixed lymphocytes from a healthy HIV-negative child were used. The results suggest important roles for UK in regulation of lymphocyte surface markers in general and in CD3- and CD19-dependent lymphocyte activation pathways specifically. Furthermore, these studies add to a widening body of evidence implicating UK dysregulation in the pathogenesis of HIV disease and may point to pharmacological opportunities involving UK to delay or prevent progression of HIV infection into full-blown AIDS. J. Leukoc. Biol. 64: 198–202; 1998.
SB202190, a selective inhibitor of p38 mitogen-activated protein kinase, is a powerful regulator of LPS-induced mRNAs in monocytes
Authors: Manthey Carl L , Wang Shen-Wu , Kinney Stephen D , Yao Zhengbin 
Published: January 2018

Abstract
Inhibitors of p38 mitogen-activated protein kinase (p38) have been reported to block tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) production in monocytes at the level of mRNA translation. Yet, several studies document that p38 can phosphorylate and activate specific transcription factors. Thus, to understand better the role of p38 during monocyte activation, we sought to determine the extent to which p38 is required for lipopolysaccharide (LPS)-induced gene expression. For this, differential mRNA display was used to identify LPS-induced genes whose expression was blocked by SB202190, a specific inhibitor of p38. A partial screen identified 10 genes in monoyctes induced 4- to 74-fold by LPS. Of these, genes encoding interferon-induced gene 15, neuroleukin, radiation-inducible immediate-early gene-1, A20, IL-1β, and superoxide dismutase were suppressed &gt;50% by SB202190. LPS-induced gene activation was not blocked by cycloheximide, indicating that synthesis of intermediate proteins was not required. SB202190 blocked gene induction by 50% when present between 41 and 123 nM, consistent with the potency of this compound as a p38 inhibitor. Furthermore, the ability of SB202190 to block gene activation was stimulus-dependent. LPS and interferon-α (IFN-α) both up-regulated neuroleukin mRNA, but only LPS-induced neuroleukin mRNA was suppressed by SB202190. In contrast, TNF-α and LPS both induced IL-8 mRNA, and induction by either TNF-α or LPS was blocked by SB202190. These data were consistent with the ability of LPS and TNF-α, but not IFN-α, to activate p38 in monocytes. The results provide pharmacological evidence that p38 may be a key mediator of inducible gene expression in monocytes, but its role is stimulus and gene specific. J. Leukoc. Biol. 64: 409–417; 1998.
The murine neutrophil-chemoattractant chemokines LIX, KC, and MIP-2 have distinct induction kinetics, tissue distributions, and tissue-specific sensitivities to glucocorticoid regulation in endotoxemia
Authors: Rovai Leonor E , Herschman Harvey R , Smith Jeffrey B 
Published: January 2018

Abstract
Lipopolysaccharide-induced CXC chemokine (LIX) is a novel murine neutrophil-chemoattractant CXC chemokine cloned as a glucocorticoid-attenuated response gene. We investigated LIX message expression in an acute endotoxemia model. LIX message peaks later than KC or macrophage inflammatory protein-2 (MIP-2) and remains elevated longer in almost all tissues. Induced LIX message expression in heart is 5- to 6-fold greater than in lung and spleen, and 20-fold greater than in liver. In contrast, KC expression is equal in heart, lung, and liver, whereas MIP-2 expression is strongest in the lung. Glucocorticoid regulation of these genes also differs. Endotoxemia-induced LIX message expression in the lung is markedly enhanced in adrenalectomized mice and strongly attenuated by dexamethasone, whereas lung KC and MIP-2 expression are unaffected by glucocorticoids. It is surprising to note that endotoxemia-induced brain expression of LIX (but not KC or MIP-2) is increased by dexamethasone. These observations suggest that LIX may have biological roles distinct from KC and MIP-2. J. Leukoc. Biol. 64: 494–502; 1998.
Activation of mitogen-activated protein kinase cascades during priming of human neutrophils by TNF-α and GM-CSF
Authors: McLeish Kenneth R , Knall Cindy , Ward Richard A , Gerwins Par , Coxon Patricia Y , Klein Jon B , Johnson Gary L 
Published: January 2018

Abstract
The signal transduction pathways activated by tumor necrosis factor α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF) that lead to priming of polymorphonuclear leukocytes (PMNs) are unknown. The hypotheses that these cytokines stimulate multiple mitogen-activated protein kinase (MAPK) cascades, including extracellular signal-regulated kinases (ERKs), c-Jun amino-terminal kinases (JNKs), and p38 MAPK, and that these MAPKs participate in priming of human PMNs were examined. TNF-α stimulated a dose-dependent increase in ERK and p38 MAPK activities that was maximal at 10 min. JNKs were not stimulated by TNF-α or GM-CSF. GM-CSF stimulated ERK activity comparable to that of TNF-α, but GM-CSF was a less potent stimulus of p38 MAPK activity. The tyrosine kinase inhibitor, genistein, inhibited ERK and p38 MAPK stimulation by both cytokines. The phosphatidylinositol 3-kinase inhibitor, wortmannin, attenuated stimulation of ERKs and p38 MAPK by GM-CSF, but not TNF-α. GM-CSF, but not TNF-α, stimulated wortmannin-sensitive activation of Raf-1. TNF-α and GM-CSF priming of superoxide release stimulated by N-formyl-methionyl-leucyl-phenylalanine was significantly attenuated by the MEK inhibitor, PD098059, and the p38 MAPK inhibitor, SB203580. Incubation with both MAPK inhibitors produced an additive effect. Our data suggest that TNF-α and GM-CSF activate ERKs and p38 MAPK by different signal transduction pathways. Both ERK and p38 MAPK cascades contribute to the ability of TNF-α and GM-CSF to prime the respiratory burst response in human PMNs. J. Leukoc. Biol. 64: 537–545; 1998.