bluuebunny/crossref_metadata_2025_split huggingface dataset:
The CD14 differentiation antigen mediates the development of endotoxin responsiveness during differentiation of mononuclear phagocytes
Authors: Martin Thomas R , Mongovin Stephen M , Tobias Peter S , Mathison John C , Moriarty Ann M , Leturcq Didier J , Ulevitch Richard J 
Published: January 2018

Abstract
The CD14 antigen was originally described as a differentiation antigen on mononuclear cells. The purpose of this study was to investigate the relationship between the appearance of surface CD14 and the acquisition of lipopolysaccharide (LPS) responsiveness during maturation of mononuclear phagocytes. Immature THP-1 cells responded poorly to LPS in the absence or presence of serum. Treatment with the maturational agent calcitriol caused a dose- and time-dependent increase in CD14 mRNA and surface CD14 and enhanced the responsiveness of THP-1 cells to smooth and rough form LPS, complexes of LPS and lipopolysaccharide-binding protein (LBP), and LPS in low concentrations of serum. Monoclonal antibodies to CD14 blocked the responses of THP-1 to LPS, LPS-LBP complexes and LPS in serum. Immunodepletion of LBP from serum also inhibited the effect of LPS in serum. The data show that maturation of the response of THP-1 cells to LPS and LPS-LBP complexes depends on the appearance of CD14 on the cell surface. Maturation of the response to LPS in serum depends in large part on the appearance of CD14 on the cell surface and the presence of LBP in serum. J. Leukoc. Biol. 56: 1–9; 1994.
In vivo endotoxin exposure increases neutrophil counts without maintenance of primed superoxide anion release in short-term cultures of sheep bone marrow
Authors: Carey Lisa A , Albertine Kurt H , Gee Marlys H 
Published: January 2018

Abstract
A short-term bone marrow culture was established to determine the functional and proliferative responses of neutrophils sampled from sheep exposed to endotoxin in vivo. Iliac crest bone marrow was drawn from surgical control animals and from sheep given a 12-h infusion of endotoxin. In these bone marrow aspirates, neutrophils from endotoxin-treated sheep showed primed superoxide anion release compared with controls when stimulated with phorbol myristate acetate. Priming was no longer present in neutrophils tested after 2 days in culture. The neutrophil cell count, however, was higher after 2 days in culture than in controls. Increased neutrophil production/viability was reproduced in naive bone marrow cultures by replacing part of the normal serum medium with plasma taken from sheep several hours after endotoxin infusion. These data suggest that a dissociation exists between priming and increased neutrophil production/viability in response to endotoxin. J. Leukoc. Biol. 56: 145–150; 1994.
Dysregulation of cytokine expression in monocytes from HIV-positive individuals
Authors: Lathey Janet L , Kanangat Siva , Rouse Barry T , Agosti Jan M , Spector Stephen A 
Published: January 2018

Abstract
Because HIV may alter the production of inflammatory factors produced by monocytes, the expression of tumor necrosis factor α (TNF-α), tissue factor (TF), interleukin (IL)-1β, and IL-6 was evaluated in 47 HIV-seropositive persons and seronegative control subjects. RNA was extracted from freshly isolated lipopolysaccharide (LPS)-stimulated or unstimulated monocytes. Cytokine and TF expression was quantitated by dot blot hybridization or a reverse transcription polymerase chain reaction (RT-PCR). A significant depression of TF mRNA was observed in LPS-stimulated monocytes (66% less in AIDS, 20% less in AIDS-related complex (ARC), and 0% less in asymptomatic patients), whereas normal responses were observed for TNF-α, IL-1β, and IL-6. When constitutive expression was measured in unstimulated monocytes by RT-PCR, a differential pattern was also observed. TNF-α and IL-1β were positive in 85% of asymptomatic persons, compared with only 27% of ARC and 42% of AIDS patients. Expression of IL-6 was observed in lower proportions, 27-30%, with no significant differences among disease states. All samples were negative for TF. Thus, the regulation of inflammatory molecules is differentially altered in individuals with HIV infection. TF is preferentially down-regulated, compared with TNF-α, IL-1β, and IL-6, in LPS-stimulated monocytes as patients progress to AIDS. TNF-α and IL-1β are preferentially up-regulated, compared with IL-6 and TF, in unstimulated monocytes in asymptomatic persons, with a loss of up-regulation as patients progress to AIDS. J. Leukoc. Biol. 56: 347–352; 1994.
Inhibition of T cell adhesion to extracellular matrix glycoproteins by histamine: a role for mast cell degranulation products
Authors: Hershkoviz Rami , Lider Ofer , Baram Dana , Reshef Tamar , Miron Shmuel , Mekori Yoseph A 
Published: January 2018

Abstract
Mast cells, which are capable of releasing a multitude of preformed and newly generated biological mediators and cytokines, are involved in various inflammatory processes. We studied whether histamine, a mast cell degranulation product, influences the adhesive interactions of T cells with extracellular matrix (ECM) glycoproteins, an event that occurs at sites of inflammation and is mediated primarily by virtue of cell-surface receptors of the β1-integrin subfamily. A prerequisite of lymphocyte-ECM interactions is activation of the cells, which modulates the affinity of the otherwise inactive integrins. Isolated rat CD4+ T cells were preincubated with histamine and activated with phorbol myristate acetate (PMA), and their ability to adhere to immobilized ECM components (fibronectin and laminin) was determined. Preincubation with histamine resulted in a 40–50% decrease in the adhesion of the CD4+ cells to both fibronectin or laminin. The notion that inhibition of T cell adhesion to ECM proteins by histamine-induced increase of the cells’ intracellular levels of cAMP, thus interfering with calcium influx-associated events that occur during T cell activation, is supported by the finding that T cell adhesion was also abrogated by pharmacological inducers of cAMP. When the T cells were preincubated with supernatants of immunologically activated mast cells and then activated with PMA, a 40–50% inhibition of their adhesion to fibronectin or laminin was also observed. The inhibitory moiety present in the mast cell degranulation supernatants was resistant to heat (80°). Histamine exerted its suppressive effect on adhesion of T cells via their H2 receptors, as pretreatment with H2 antagonists abrogated the inhibitory effect. Thus, both purified histamine and mast cell-secreted histamine appear to be capable of affecting T cell interactions with ECM. J. Leukoc. Biol. 56: 495–501; 1994.
Induction of superoxide anion production from monocytes and neutrophils by activated platelets through the P-selectin–sialyl Lewis X interaction
Authors: Tsuji Tsutomu , Nagata Kisaburo , Koike Junzo , Todoroki Naoko , Irimura Tatsuro 
Published: January 2018

Abstract
Activated platelets expressing P-selectin on their surface are known to adhere to monocytes and neutrophils. We examined the possibility that the leukocytes were activated by their adhesion to activated platelets and demonstrated that P-selectin–dependent platelet adhesion to neutrophils and monocytes induced production of extracellular superoxide anion (O2-) by these leukocytes. Leukocyte membrane glycoproteins containing Ser/Thr-linked carbohydrate chains were responsible for the signal reception leading to the leukocyte activation. Cytokines were shown to influence these processes. For example, treatments of neutrophils with interleukin-8 (IL-8) or granulocyte colony-stimulating factor (G-CSF) potentiated the P-selectin-induced O2- production. Furthermore, interleukin-1 (IL-1) and interferon-γ (IFN-γ) induced surface expression of P-selectin on platelets in the presence of a low concentration of thrombin and consequently enhanced their adhesion capacity to leukocytes. These results indicated that the adhesion of activated platelets to the leukocytes through the interaction between P-selectin and its carbohydrate ligand, sialyl Lewis X (Lex), was a crucial step for the activation of leukocyte function and supported the notion that activated platelets were actively involved in the inflammatory processes. J. Lcukoc. Biol. 56: 583–587; 1994.
In vitro and in vivo effects of pentoxifylline on macrophages and lymphocytes derived from autoimmune MRL-lpr/lpr mice
Authors: Hecht Matthias , Müller Meike , Lohmann-Matthes Marie-Luise , Emmendörffer Andreas 
Published: January 2018

Abstract
MRL-lpr/lpr mice develop an autoimmune disease similar to human systemic lupus erythematosus (SLE). The main characteristics of this disease are increasing autoantibody formation, elevated plasma levels of immune complexes, a massive lymphoproliferation, a rising proteinuria, and arthritic symptoms. Finally, the mice die at an age of about 6 months due to a fatal immune complex glomerulonephritis. Macrophages are involved in the development of SLE due to their functions as antigen-presenting as well as cytokine-producing cells. T and B cells are involved in the disease by secreting cytokines and producing antibodies. Pentoxifylline (PTX), a xanthine derivative, is known to exert different effects on functions of leukocytes and erythrocytes and has been used in clinical studies, e.g., in septic shock syndrome. In our studies we first investigated the in vitro effect of PTX on macrophages and lymphocytes derived from MRL-lpr mice. Our investigations concerning production of superoxide anion and TNF-α by LPS and/or IFN-γ activated bone marrow and peritoneal macrophages, MHC class II expression on these cells, and the proliferative capacity and Il-2 production of mitogen activated lymphocytes, revealed that PTX reduces the activation and the inflammatory response of these cells. Based on these results, we further investigated the effect of in vivo treatment with PTX. MRL-lpr mice treated with PTX showed diminished proteinuria, reduced titer of dsDNA-autoantibodies in the plasma and an increased survival rate. Our data clearly demonstrate that PTX is able to diminish the severity of the disease and to prolong the life of MRL-lpr/lpr mice. J. Leukoc. Biol. 57: 242–249; 1995.
Free-form neutrophil elastase is an independent marker predicting recurrence in primary breast cancer
Authors: Yamashita Jun-ichi , Ogawa Michio , Shirakusa Takayuki 
Published: January 2018

Abstract
We have measured the immunoreactive neutrophil elastase (ir-NE) concentration in tumor extracts of 313 primary human breast cancers using an enzyme-linked immunosorbent assay recently developed and have evaluated its association with disease-free survival. This is a sensitive assay that enables rapid measurement of both free-form and α1-proteinase inhibitor (α1-PI)–complexed form of ir-NE. Breast cancer patients with high ir-NE concentrations had a significantly shorter disease-free survival (P = .013) than those with a low ir-NE concentration at the cutoff point of 9.0 μg/100 mg protein, which was determined in another group of 49 patients. In multivariate analysis, the ir-NE level was found to be an independent prognostic factor (relative risk = 2.2, P = .025) for disease recurrence in human breast cancer. Furthermore, when multivariate analysis was repeated with inclusion of each level of free-form and α1-PI-complexed form, the former level was an independent predictor of recurrence (relative risk = 2.5, P = .015), whereas the latter was not independently predictive (P = .43). These results support the hypothesis that this enzyme may play an active role in the tumor progression that leads to metastasis in human breast cancer. J. Leukoc. Biol. 57: 375–378; 1995.
C1q triggers neutrophil superoxide production by a unique CD18-dependent mechanism
Authors: Goodman Elaine B , Anderson Donald C , Tenner Andrea J 
Published: January 2018

Abstract
Complement protein C1q induces the production of superoxide (O2-) by neutrophils via an as yet unidentified receptor or receptor complex. Several strategies were therefore used to identify cell surface molecules involved in the response of neutrophils to C1q and its collagen-like domain (C1q-CLR). Treatment of neutrophils with phosphatidylinositol-specific phospholipase C effectively removed the phosphatidylinositol-linked surface molecules CD14 and CD16, yet did not reduce Of production in response to C1q. Next, 17 monoclonal antibodies (mAbs) recognizing various neutrophil surface antigens were tested for their ability to inhibit C1q-CLR-mediated O2- production. Only two of the mAbs, 44a and IB4, which recognize CD11b/CD18 (complement receptor 3 or Mac-1), were inhibitory. In addition, neutrophils from a patient with leukocyte adhesion deficiency, which are CD18 deficient, did not produce Of in response to C1q or C1q-CLR. Because CD11b/CD18 is recognized to play a role in cell adhesion, the role of adherence in C1q-mediated O2- production was explored. Adherence of neutrophils to C1q-CLR-coated surfaces occurred with kinetics, which usually paralleled those of O2- production, and was invariably abolished by the anti-CD11b mAb 44a. However, this mAb often only partially inhibited O2- production, indicating that an avid attachment of neutrophils to the C1q-CLR-coated surface is not required for O2- production. J. Leukoc. Biol. 58: 168–176; 1995.
Alveolar macrophages as a cell source of cytokine hyperproduction in HIV-related interstitial lung disease
Authors: Agostini Carlo , Sancetta Rosaria , Cerutti Andrea , Semenzato Gianpietro 
Published: January 2018

Abstract
Pulmonary macrophages play an important role in the pathogenesis of the acquired immunodeficiency syndrome (AIDS). They are known to be discrete target cells for human immunodeficiency virus (HIV), and compelling evidence is accumulating that alveolar macrophages (AMs) from HIV-infected patients behave as versatile secretory cells that, acting as antigen-presenting cells, release a great variety of cytokines. The secretory products of AMs, pivotal to their immune effects, may contribute to localized immune dysregulation as well as to primary lung damage and clinical disease. Pulmonary macrophages are also thought to facilitate retroviral spread by their direct infection, by presenting HIV antigens to uninfected T cells, and by secreting cytokines that trans-activate HIV expression. This review briefly considers the events underlying the role of AMs in the pulmonary defense mechanisms against HIV and AIDS-related opportunistic infections. Following a brief overview of immune mechanisms taking place in the lungs of HIV-infected subjects, we describe the specific role of AMs in the immune mechanisms devoted to recognizing and removing HIV-infected cells and controlling the local growth of opportunists. The pathogenetic role envisaged for macrophages in lung damage are also reviewed in the context of the known biology of these cells. Finally, this review examines the relevance of the retroviral infection of AMs in terms of pathogenesis of the HIV-related interstitial lung disease.
Temporal sequence of pulmonary cytokine gene expression in response to endotoxin in C3H/HeN endotoxin-sensitive and C3H/HeJ endotoxin-resistant mice
Authors: Nill Michael R , Oberyszyn Tatiana M , Ross Mary S , Oberyszyn Andrew S , Robertson Fredika M 
Published: January 2018

Abstract
Although previous studies suggested that tumor necrosis factor alpha (TNF-α) was a critical cytokine responsible for the inflammation observed after exposure to endotoxin, other mediators may also play an important role in the regulation of systemic inflammatory responses independent of TNF-α. The present study compared the temporal sequence of endotoxin-induced TNF-α, interleukin-1α (IL-1α), and interleukin-10 (IL-10) gene expression and cellular localization of cytokine proteins in pulmonary tissue of two strains of mice that have a genetically based differential sensitivity to endotoxin. Lung tissue and plasma were harvested from endotoxin-sensitive C3H/HeN and endotoxin-resistant C3H/HeJ micé at 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, and 24 h after intraperitoneal (i.p.) injection of 5 mg/kg endotoxin (Escherichia coli–derived lipopolysaccharide, serotype 0111:B4). There were significant elevations in both TNF-α gene and IL-2α expression immediately (15 min) after endotoxin injection in C3H/HeN mice. Although levels of TNF-α mRNA in the two mouse strains were similar at 1-2 h, the IL-1α gene expression in pulmonary tissue isolated from endotoxin-resistant mice was not comparable to the levels detected in C3H/HeN endotoxin-sensitive mice at the same times. The most dramatic difference in endotoxin-induced cytokine gene expression between the two strains of mice was in IL-10 mRNA levels in pulmonary tissue isolated from endotoxin-sensitive mice, compared to the lack of detectable increase in IL-10 gene expression in C3H/HeJ endotoxin-resistant mice above baseline at any time point examined. Quantitation of neutrophil infiltration into pulmonary tissue using immunochemical detection of CR-1, a myeloid differentiation-specific antibody, demonstrated that there was a significantly decreased inflammatory infiltrate in pulmonary tissue isolated from C3H/HeJ mice following endotoxin administration, which correlated with decreased levels of proinflammatory cytokine immunoreactive protein within pulmonary cells. Pulmonary cytokine synthesis and immunoreactive protein production did not directly correlate with either the magnitude or the temporal sequence of increases in plasma cytokine levels, suggesting that systemic levels of cytokines may not accurately reflect the cytokine response within the local tissue milieu. The present observations demonstrate that the differential synthesis and production of immunosuppressive cytokines as well as proinflammatory cytokines may be important variables in the determination of the extent of infiltration of inflammatory cells into the local pulmonary site in response to endotoxin and may significantly contribute to the determination of sensitivity or resistance to endotoxin in this murine model.
Macrophage apoptosis in the absence of active interleukin-1β-converting enzyme
Authors: Nett-Fiordalisi Michelle , Tomaselli Kevin , Russell John H , Chaplin David D 
Published: January 2018

Abstract
The interleukin-1β converting enzyme (ICE) is the cysteine proteinase responsible for cleaving the 31-kDa interleukin-1β (IL-1β) precursor to its active 17-kDa form. In lipopolysaccharide-stimulated cultured macrophages, induction of apoptosis but not necrosis effectively induces conversion of the IL-1β precursor to its mature form and results in the concomitant release of the mature cytokine from the cell. To determine whether ICE activity is required for macrophage apoptosis, we have exposed macrophages either to 5 mM ATP or to alloreactive cytolytic T lymphocytes (CTL) in the absence and presence of the ICE inhibitor peptide YVAD-chloromethylketone (YVAD-cmk). Activated cells treated with YVAD-cmk and ATP or CTL showed no mature IL-1β in either the cell lysates or the culture supernatants, indicating effective inhibition of ICE activity; however, the YVAD-treated macrophages showed no detectable change in 51Cr release or nuclear fragmentation, indicating failure to inhibit apoptotic cell death. Thus, in these cells, YVAD-cmk uncouples IL-1β processing and apoptosis.
Activation and regulation of chemokines in allergic airway inflammation
Authors: Lukacs N W , Strieter R M , Chensue S W , Kunkel S L 
Published: January 2018

Abstract
Allergic airway inflammation is characterized by peribronchial eosinophil accumulation within the submucosa surrounding the airway. The initial induction of immunoglobulin E (IgE)-mediated mast cell degranulation, up-regulation of adhesion molecules, and the production of inflammatory and chemotactic cytokines, leading to the infiltration of specific leukocyte subsets, is orchestrated in a sequential manner. The activation and degranulation of local mast cell populations is an immediate airway response mediated both by antigen-specific, surface bound IgE and by cytokine-induced activational pathways. Subsequently the infiltration and activation of effector leukocytes (neutrophils and eosinophils) mediated by the persistant activation of allergen-specific T cells leads to pathological manifestations within the lung and airway. The development of appropriate animal models to dissect the critical mechanisms involved in antigen-induced airway pathology is crucial for the development of efficacious therapies. We have utilized a model of allergic airway inflammation induced by intratracheal challenge with parasite (Schistosoma mansoni) egg antigen in presensitized mice. This model has proven useful in the assessment of eosinophil recruitment and has identified key cytokines involved in leukocyte elicitation. These cytokines include interleukin-4 and tumor necrosis factor, which appear to act as early response mediators, as well as C-C chemokines, macrophage inflammatory protein-1a, and RANTES, which act directly on eosinophil recruitment. In addition, we have found that both C-X-C and C-C chemokines are expressed in pulmonary-derived mast cells, suggesting an important contribution to leukocyte responses in the allergic airway.
Human CD14+ leukocytes acquire the phenotype and function of antigen-presenting dendritic cells when cultured in GM-CSF and IL-4
Authors: Kiertscher Sylvia M , Roth Michael D 
Published: January 2018

Abstract
The combination of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) induces the growth of antigen-presenting cells (APC) from adherent peripheral blood leukocytes. These cells have been characterized as dendritic cells (DC), yet many questions exist regarding their relationship to other DC populations and the nature of their progenitors. To address these issues, we utilized a combination of immunomagnetic depletion, cell sorting, and cell culture to isolate four distinct APC populations; macrophages expressing high levels of CD14 (CD14bright macrophages), DC produced by culturing adherent cells in GM-CSF and IL-4 (cultured DC), and two different subsets of fresh DC that express low levels of CD14 (CD14dim DC). Each population exhibited a unique morphology and a unique profile of cell surface markers. In contrast to macrophages, all three DC populations expressed the DC marker CD83, as well as high levels of MHC molecules and the costimulatory molecules B7-1 (CD80) and B7-2 (CD86). In addition, all three DC populations presented soluble tetanus toxin antigen and stimulated T cell proliferation to levels far superior to that of macrophages. Blocking studies demonstrated a costimulatory role for B7-1, B7-2, and CD40 in antigen presentation, although B7-2 expression was the single most important factor. To identify the progenitors of cultured DC, we sorted the adherent fraction of PBMC into discrete subpopulations prior to exposure to GM-CSF and IL-4. DC activity derived entirely from CD14+ precursors and was equally demonstrable using either the CD14dim or CD14bright subsets. Although these DC precursors lost expression of CD14 in culture, they maintained most of their other myeloid features. We conclude that human CD14+ leukocytes acquire the phenotype and function of DC when cultured in GM-CSF and IL-4.