bluuebunny/crossref_metadata_2025_split huggingface dataset:
1α,25-Dihydroxyvitamin D3 promotes monocytopoiesis and suppresses granulocytopoiesis in cultures of normal human myeloid blast cells
Authors: Barton Aisling E , Bunce Christopher M , Stockley Robert A , Harrison Paul , Brown Geoffrey 
Published: January 2018

Abstract
Primitive myeloid blast cells (2-10 106) were purified from 18–22-week fetal liver–derived mononuclear cell preparations by negative selection followed by counterflow cell elutriation. The cells, when maintained in liquid culture in the presence of 100 U/ml interleukin-3 (IL-3) for the first 5 days and 10 U/ml IL-3 and 30 ng/ml granulocyte colony-stimulating factor thereafter, underwent considerable proliferation resulting in an ~ 30-fold increase in cell number by day 14. Analyses of cell morphology and of the numbers of cells that expressed the neutrophil-associated antigen CD15, the monocyte-associated antigen 61D3, and enzymes α-naphthyl acetate esterase (ANAE), human leukocyte elastase, and cathepsin G revealed that proliferation of the cells was associated with their concomitant differentiation toward neutrophils and monocytes. The cultures generated predominantly neutrophils; by day 14, wells seeded with 2 105 cells produced ~ 5 106 neutrophils as opposed to only ~ 3.5 105 cells with a monocytoid morphology. This predominance of granulocytopoiesis over monocytopoiesis was confirmed by the numbers of cells that had acquired expression of the CD15 antigen and ANAE, which were approximately 2 106 and 1 105, respectively. By contrast, parallel cultures containing 100 nM 1α,25-dihydroxyvitamin D3 (VitD3) generated more monocytes than neutrophils. At day 14, VitD3-treated cultures contained ~2 106 cells with morphologies consistent with their differentiation toward monocytes and ~ 1 106 ANAE-positive cells, compared with ~ 9.5 105 cells having morphologies of granulocyte-series cells and ~ 4.5 104 CD15-positive cells. In both control and VitD3-treated cultures, the enzymes cathepsin G and human leukocyte elastase were expressed almost exclusively by cells that were differentiating toward neutrophils. These data reveal that VitD3 promotes monocytopoiesis and suppresses granulocytopoiesis of primitive blast cells. J. Leukoc. Biol. 56: 124–132; 1994.
13-HODE inhibits the intracellular calcium increase of activated human polymorphonuclear cells
Authors: van de Velde Marco J , Engels Ferdi , Henricks Paul A J , Nijkamp Frans P 
Published: January 2018

Abstract
We studied the effect of the linoleic acid metabolite 13-hydroxyoctadecadienoic acid (13-HODE) on the increase of the intracellular calcium concentration, [Ca2+]i, induced by platelet-activating factor (PAF), leukotriene B4 (LTB4), and formyl-Met-Leu-Phe (fMLP) in human polymorphonuclear leukocytes (PMNs). 13-HODE by itself did not change the [Ca2+]i of PMNs. However, when PMNs were preincubated with 13-HODE and subsequently stimulated with PAF, LTB4, or fMLP, an inhibition of the increase of the [Ca2+]i was observed. The PAF-induced calcium response was concentration-dependently inhibited between 0.1 and 5 μM 13-HODE. These results suggest that 13-HODE can affect the increase of the [Ca2+]i and hence can modulate activation of PMNs. J. Leukoc. Biol. 56: 200–202; 1994.
Gene therapy: current status and future prospects
Authors: Kerr William G , Mulé James J 
Published: January 2018

Abstract
The ability to successfully introduce foreign genes into eukaryotic cells has made possible a new approach to the treatment of human disease. Gene therapy is now being brought to bear on genetic, malignant, and infectious diseases. In this review, we summarize the status of the field through an analysis of clinical protocols involving transfer of marker or therapeutic gene(s) into various somatic cell targets. Many of these trials will begin to examine whether or not patients with diseases that are unresponsive to conventional therapeutic interventions (e.g., pharmaceutical, surgical) will show benefit solely from somatic cell-based gene therapies. In other trials, the gene therapies are meant to complement or bolster the effect of conventional treatments. Although the field of gene therapy is now entering the clinical arena, we will also attempt to summarize certain shortcomings and technical hurdles that will need to be overcome for its eventual widespread use. J. Leukoc. Biol. 56: 210–214; 1994.
The neuropathogenesis of HIV-1 infection
Authors: Gendelman Howard E , Lipton Stuart A , Tardieu Marc , Bukrinsky Michael I , Nottet Hans S L M 
Published: January 2018

Abstract
HIV infection in brain revolves around productive viral replication in cells of mononuclear phagocyte lineage, including brain macrophages, microglia, and multinucleated giant cells [1–4]. Together, they are the instigators for cellular and viral neurotoxic activities [5–10]. Several published reports show that viral and/or cellular products produced from HIV-1-infected macrophages injure neurons and induce glial proliferation during advancing central nervous system (CNS) infection [11–18]. These findings are supported by the apparent discrepancy between the distribution and numbers of virus-infected cells and concomitant brain tissue pathology [5, 19]. Whether these soluble factors are indirectly responsible for neuronal damage remains undefined. The identification and regulation of neurotoxins produced from HIV-infected macrophages are central to uncovering how HIV mediates CNS disease. The authors who contributed to this work represent laboratories with overlapping areas of expertise. Broad-based complementary hypotheses regarding HIV neuropathogenesis are now provided. J. Leukoc. Biol. 56: 389–398; 1994.
Cytokine networks in solid human tumors: regulation of angiogenesis
Authors: Leek R D , Harris A L , Lewis C E 
Published: January 2018

Abstract
The isolation, purification, and molecular cloning of an increasing number of cytokines and their receptors have allowed major advances in our understanding of the relevance of these proteins to the pathobiology and treatment of such human diseases as neoplasia. Cytokines produced by the multiple cell types present within the microenvironment of solid tumors form a complex, dynamic network, in which they have overlapping properties, induce other cytokines and alter the expression of soluble and cell surface-bound cytokine receptors. A broad number of such intratumoral cytokines have multiple effects on tumor progression. These include direct and indirect effects both on tumor cell growth and metastatic behaviors and on such cells in the stromal compartment as fibroblasts, infiltrating immune cells, and endothelial cells in the microvasculature. Here, we review the sites of production and multifaceted role of several key cytokines in the stimulation of a new blood supply within growing neoplasms. The clinical implications and new therapeutic targets suggested by this rapidly emerging picture of the cellular and molecular mechanisms subserving tumor angiogenesis are also discussed. J. Leukoc. Biol. 56: 423–435; 1994.
Coengagement of CD2 with LFA-1 or VLA-4 by bispecific ligand fusion proteins primes T cells to respond more effectively to T cell receptor-dependent signals
Authors: Dietsch Mary T , Chan Po-Ying , Kanner Steven B , Gilliland Lisa K , Ledbetter Jeffrey A , Linsley Peter S , Aruffo Alejandro 
Published: January 2018

Abstract
To examine the effects of ligand engagement and accessory molecule juxtaposition on T cell receptor (TCR) signaling, we prepared LFA-3/ICAM-1 Rg and LFA-3/VCAM-1 Rg bispecific immunoglobulin fusion proteins (Rg, recombinant globulin). These novel fusion proteins allowed us to examine the effects of ligand driven co-engagement of T cell proteins CD2 and LFA-1 or CD2 and VLA-4 on TCR-dependent mobilization of intracellular Ca2+. We observed that preincubation of resting T cells with LFA-3/ICAM-1 Rg or LFA-3/VCAM-1 Rg fusion proteins resulted in significantly enhanced mobilization of intracellular Ca2+ following TCR-accessory molecule cross-linking relative to T cells preincubated with each of the monospecific Rgs alone or with combinations of the monospecific Rg fusion proteins. In addition, such coengagement stimulated TCR-dependent activation and tyrosine phosphorylation of phospholipase Cγ1 (PLCγ1). These results suggest that when T cells interact with antigen presenting cells the engagement of multiple cell adhesion molecules such as CD2, LFA-1, and VLA-4 primes the T cell to respond more effectively to signals delivered through the TCR. J. Leukoc. Biol. 56: 444–452; 1994.
Production of nitric oxide and peroxynitrite in the lung during acute endotoxemia
Authors: Wizemann Theresa M , Gardner Carol R , Laskin Jeffrey D , Quinones Susan , Durham Steven K , Goller Nancy L , Ohnishi S Tsuyoshi , Laskin Debra L 
Published: January 2018

Abstract
Nitric oxide is a short-lived cytotoxic mediator that has been implicated in the pathogenesis of endotoxin-induced tissue injury and septic shock. In the present studies we determined whether this mediator is produced in the lung during acute endotoxemia. We found that intravenous injection of rats with bacterially derived lipopolysaccharide (LPS), a condition that induces acute endotoxemia, caused a time-dependent increase in inducible nitric oxide synthase (iNOS) mRNA expression in the lung, which reached a maximum after 24 h. This was correlated with nitric oxide production in the lung as measured by electron paramagnetic spin trapping, which was detectable within 6 h. Alveolar macrophages (AMs) and interstitial macrophages (IMs) isolated from rats 6–12 h after induction of acute endotoxemia were also found to exhibit increased nitric oxide production in response to in vitro stimulation with interferon-γ (IFN-γ) and LPS measured by nitrite accumulation in the culture medium. The effects of acute endotoxemia on nitric oxide production by these cells were, however, transient and returned to control levels by 24 h in AMs and 36 h in IMs. Interestingly, although nitrite accumulation in the culture medium of IMs isolated 48 h after induction of acute endotoxemia and stimulated with low concentrations of IFN-γ and LPS was reduced, when compared with cells from control animals, these cells, as well as AMs, continued to express high levels of iNOS protein and mRNA. This was correlated with increased peroxynitrite production by the cells. Peroxynitrite has been shown to act as a nitrating agent and can generate nitrotyrosine residues in proteins. Using a specific antibody and immunohistochemistry, we found evidence of nitrotyrosine residues in sections of lungs 48 h after treatment of rats with endotoxin. These data suggest that nitric oxide produced by IMs and AMs can react with superoxide anion to form peroxynitrite. Taken together, the present studies demonstrate that AMs and IMs are activated following acute endotoxemia to produce reactive nitrogen intermediates and that both cell types contribute to inflammatory responses in the lung. J. Leukoc. Biol. 56: 759–768; 1994.
Identification of a proline-arginine-rich antibacterial peptide from neutrophils that is analogous to PR-39, an antibacterial peptide from the small intestine
Authors: Shi Jishu , Ross Christopher R , Chengappa M M , Blecha Frank 
Published: January 2018

Abstract
Neutrophil nonoxidative defense mechanisms include several low molecular weight antimicrobial peptides. We have isolated a proline-arginine-rich antibacterial peptide from porcine neutrophils. This cationic, low molecular weight peptide has a very high degree of identity (97%) to a bactericidal peptide, PR-39, that has been found in the porcine small intestine. Isolation of the same antimicrobial peptide from both neutrophils and cells of the small intestine in the same species is unique and suggests an important role for this protein in innate immune defenses. J. Leukoc. Biol. 56: 807–811; 1994.
Neuropeptide-mediated regulation of hapten-specific IgE responses in mice I. Substance P-mediated isotype-specific suppression of BPO-specific IgE antibody-forming cell responses induced in vivo and in vitro
Authors: Carucci John A , Auci Dominick L , Herrick Christina A , Durkin Helen G 
Published: January 2018

Abstract
The ability of substance P (SP) to regulate peak benzyl-penicilloyl (BPO)-specific IgE antibody-forming cell (AFC) responses in vivo and the ability of SP and other neuropeptides to regulate BPO-specific memory IgE AFC responses induced in vitro was determined. SP injected subcutaneously into BPO-keyhole limpet hemocyanin (BPO-KLH)-sensitized mice at the time of peak IgE responses suppressed these responses within 48 h (&gt;90%). The suppression obtained was IgE isotype-specific, dose-dependent, and transient. When spleen cells from immunized mice were cultured for 5 days with BPO-KLH, peak memory IgE AFC responses were induced in vitro. Inclusion of either SP or vasoactive intestinal peptide (VIP), but not neurotensin, serotonin, somatostatin, or gastrin, in cultures suppressed these responses in isotype-specific, dose-dependent fashion (70%). SP-, but not VIP-mediated suppression of IgE responses was abrogated by inclusion of anti-IFNγ in culture. J. Leukoc. Biol. 57: 110–115; 1995.
Inhalation exposure to isobutyl nitrite inhibits macrophage tumoricidal activity and modulates inducible nitric oxide
Authors: Soderberg Lee S F , Barnett John B 
Published: January 2018

Abstract
Abuse of nitrite inhalants is common among male homosexuals and a history of abuse has been correlated with seropositivity to HIV and with the incidence of Kaposi’s sarcoma among AIDS patients. The present study shows that inhalation exposure of mice to 900 ppm isobutyl nitrite for 45 min/day for 14 days compromised macrophage tumoricidal activity by up to 40% and it remained compromised for at least 7 days after terminating exposures. The inhalation exposures did not affect tumor cell binding but did inhibit inducible nitric oxide (NO•). The NO• synthase inhibitor NG-methyl-l-arginine totally inhibited both NO• production and cytotoxicity, suggesting that reductions in NO• due to inhalant exposure may be responsible for the reduced cytotoxic activity. Exposure to the inhalant increased constitutive production of tumor necrosis factor-α (TNF-α). TNF-α has been reported to stimulate the replication of HIV and the proliferation of Kaposi’s sarcoma cells in vitro. J. Leukoc. Biol. 57: 135–140; 1995.
LPS inhibits the intracellular growth of Legionella pneumophila in thioglycolate elicited murine peritoneal macrophages by iron-dependent, tryptophan-independent, oxygen-independent, and arginine-independent mechanisms
Authors: Gebran Samir J , Yamamoto Yoshimasa , Newton Catherine , Tomioka Mitsugu , Widen Ray , Klein Thomas W , Friedman Herman 
Published: January 2018

Abstract
Thioglycolate-elicited murine macrophages from genetically susceptible A/J mice activated with lipopolysaccharide (LPS) and infected with Legionella pneumophila in vitro evince marked inhibition of intracellular growth of this bacterium. The mechanism of inhibition by LPS-activated macrophages in terms of replication of this intracellular pathogen is unclear. LPS activation of murine macrophages induced a downshift in transferrin receptor (TfR) expression and reduction in cellular iron content, and this was correlated with augmented intracellular growth of Legionella in the cells. When LPS-stimulated macrophages were first saturated with iron, partial reversion of L. pneumophila growth restriction was observed. However, an excess of exogenous L-tryptophan (Trp) did not reverse this growth inhibition, nor did supplementation of the macrophage culture medium with both iron and Trp. The antilegionella activity of the macrophages induced by LPS activation was independent of reactive oxygen intermediates (ROI), since the scavengers catalase, superoxide dismutase, mannitol, and thiourea had no effect on growth restriction. Likewise, notwithstanding the ability of LPS-activated macrophages to synthesize reactive nitrogen intermediates (RNI), which was inhibited by l-arginine analogs (NG-monomethyl-l-arginine and l-aminoguanidine), as well as by incubation in arginine-free medium, their ability to inhibit the intracellular replication of L. pneumophila was not affected. Thus, we conclude that LPS-activated macrophages inhibit the intracellular growth of L. pneumophila partially by iron-dependent, Trp-independent, and ROI- and RNI-independent mechanisms. We also suggest that additional unknown mechanisms are involved, since complete reversion was not obtained. J. Leukoc. Biol. 57: 80–87; 1995.
Chemoattractant receptor-specific differences in G protein activation rates regulate effector enzyme and functional responses
Authors: Jacobs Alfred A , Huber John L , Ward Richard A , Klein Jon B , McLeish Kenneth R 
Published: January 2018

Abstract
The hypothesis that disparate neutrophil functional responses to various chemoattractants are regulated by receptor-specific rates of G protein activation was examined in HL-60 granulocytes. The initial rates of G protein activation and the affinity of receptor-stimulated G proteins for GTPγS in HL-60 membranes stimulated by fMet-Leu-Phe, C5a, and leukotriene B4 (LTB4) differed significantly among the chemoattractants, with a rank order of fMet-Leu-Phe &gt; C5a &gt; LTB4. Equilibrium GTPγS binding showed that all three chemoattractants activated a common pool of G proteins. Stimulation of phospholipasc D activation, measured as phosphatidylethanol generation, and superoxide release in intact cells also occurred with a rank order of fMet-Leu-Phe &gt; C5a &gt; LTB+. On the other hand, the rank order of reccptor affinities for ligand and of the EC50 of chemoattractant stimulation of GTPγS binding was C5a &gt; LTB4 &gt; fMet-Leu-Phe. C5a and LTB4 receptor densities were similar but were less than formyl peptide receptor density. Graded pertussis toxin treatment proportionally reduced superoxide release and phospholipase D activation to all three chemoattractants. The results suggest that receptor-specific differences in G pro tein affinity for guanine nucleotides lead to different rates of guanine nucleotide exchange and, thereby, contribute to disparate effector enzyme and functional responses. J. Leukoc. Biol 57: 679–686; 1995.
A role for C-C chemokines in fibrotic lung disease
Authors: Smith Robert E , Stricter Robert M , Zhang Kai , Phan Sem H , Standiford Theodore J , Lukacs Nicholas W , Kunkel Steven L 
Published: January 2018

Abstract
Pulmonary fibrosis is the end point of a chronic inflammatory process characterized by leukocyte recruitment and activation, fibroblast proliferation, and increased extracellular matrix production. Previous studies of models of pulmonary fibrosis have investigated the role of cytokines in the evolution of the fibrotic response. The involvement of tumor necrosis factor and interleukin-1 in bleomycin-induced lung injury, a model of idiopathic pulmonary fibrosis, has been well established, suggesting that cytokines mediate the initiation and maintenance of chronic inflammatory lesions. However, the aforementioned cytokines alone cannot account for the recruitment and activation of specific leukocyte populations found in the bleomycin model. Recently, a family of novel proinflammatory cytokines (chemokines) was cloned and characterized, yielding many putative mediators of leukocyte functions. Macrophage inflammatory protein-1α (MIP-1α) and monocyte chemoattractant protein-1 (MCP-1) belong to the C-C chemotactic cytokine family, a group of low-molecular-weight peptides. These molecules modulate chemotaxis, proliferation, and cytokine expression in leukocyte subsets. Our group has investigated the roles of MCP-1 and MIP-1α in the bleomycin model. Both MCP-1 and MIP-1α are expressed in a time-dependent manner after bleomycin challenge, and passive immunization of these animals with either anti-MIP-1α or anti-MCP-1 antibodies attenuated leukocyte accumulation. In addition, we have identified specific cell types expressing MCP-1 or MIP-1α by in situ hybridization and immunohistochemical localization, respectively. Furthermore, our results indicate that MIP-1α expression is mediated by alveolar macrophage-derived tumor necrosis factor, identifying an important cytokine pathway in the initiation of pulmonary fibrosis. Finally, anti-MIP-1α therapy attenuated fibrosis, providing direct evidence for its involvement in fibrotic pathology. Our work has clearly established that the C-C chemokines MCP-1 and MIP-1α are expressed and contribute to the initiation and maintenance of the bleomycin-induced pulmonary lesion. J. Leukoc. Biol. 57: 782–787; 1995.
Macrophage colony stimulatory factor–activated bone marrow macrophages suppress lymphocytic responses through phagocytosis: a tentative in vitro model of Rosai-Dorfman disease
Authors: Jadus Martin R , Sekhon Sant , Barton Beverly E , Wepsic H Terry 
Published: January 2018

Abstract
NBXFO hybridoma cells produced macrophage colony-stimulating factor (M-CSF), which stimulated the growth of murine bone marrow–derived macrophages with potent suppressor activity. These macrophages suppressed lymphocyte responses to mitogens and antigens in a dose-dependent manner. Using a transwell chamber, we demonstrated that macrophages needed physical contact with the lymphocytes to suppress lymphocyte proliferation on day 1 in the concanavalin A mitogen reaction. In addition, no soluble suppressor factor was detected at that time. The number of lymphocytes disappeared with time when they were cocultured with the macrophages. Electron microscopy revealed that the macrophages phagocytosized the lymphocytes after 7 1/2 h. Dextran sulfate, heparan, and fucoidan prevented the macrophages from suppressing the lymphocytes. This phenomenon resembles the human disease sinus histiocytosis, also called Rosai-Dorfman disease, in which macrophages (histiocytes) phagocytosize autologous lymphocytes; occasionally, this disease is associated with immunological abnormalities. Thus we believe that macrophage-activating cytokines, such as M-CSF, may stimulate macrophages to phagocytose lymphocytes in vivo. J. Leukoc. Biol. 57: 936–942; 1995.