bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the Regulation of Differentiation and Function of Rat Macrophages by 1,25-Dihydroxyvitamin D3 and Dexamethasone
Authors: Shezen Elias , Goldman Rachel 
Published: January 2018

Abstract
Rat bone marrow macrophage progenitor cells develop in vitro in the presence of rat embryo fibroblast conditioned medium into colonies and clusters. 1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3) (0.12-12 nM) was found to enhance the formation of macrophage colonies and the proliferation of mononuclear phagocytes in liquid cultures of bone marrow cells (ED50 0.12-1.0 nM). Fractionation of bone marrow cells by centrifugal elutriation showed that: a) macrophage progenitors are heterogeneous in size; b) the progenitors eluted at early fractions have a lower proliferative capacity (form mainly small clusters) than those eluting at later fractions (higher counterflow velocities) which develop into macrophage colonies and c) that 1,25(OH)2D3 (at 12 nM) augments the expression of colony forming cells enriched in late eluting fractions while having a suppressive effect on expression of low proliferative potential cluster forming cells enriched in early eluting fractions. Dexamethasone was found to suppress the clonal growth of macrophage progenitor cells as well as their proliferation in liquid cultures (ED50 about 1 nM). Both dexamethasone and 1,25(OH)2D3 induced in mononuclear phagocytes of 4 d cultures an increased phagocytic capability. The data suggest a regulatory role for 1,25(OH)2D3 and glucocorticosteroids in myelopoietic processes in the rat. Furthermore, when compared with our recent findings with mouse bone marrow cells, the effects, their magnitude and concentration dependence imply genuine species differences in the responses of mice and rats to these hormones.
Frontline Science: High fat diet and leptin promote tumor progression by inducing myeloid-derived suppressor cells
Authors: Clements Virginia K , Long Tiha , Long Ramses , Figley Chas , Smith Daniel M C , Ostrand-Rosenberg Suzanne 
Published: January 2018

Abstract
Obesity is a risk factor for cancer incidence and cancer mortality. The association of obesity and cancer is attributed to multiple factors, but the tightest linkage is with the chronic, low-grade inflammation that accompanies obesity. Myeloid-derived suppressor cells (MDSC) are known facilitators of cancer progression that act by suppressing the activation and function of tumor-reactive T cells. Because MDSC quantity and function are driven by chronic inflammation, we hypothesized that MDSC may accumulate in obese individuals and facilitate tumor growth by suppressing antitumor immunity. To test this hypothesis, tumor-bearing mice on a high fat or low fat diet (HFD or LFD) were assessed for tumor progression and the metabolic dysfunction associated with obesity. HFD enhanced the accumulation of MDSC, and the resulting MDSC had both beneficial and detrimental effects. HFD-induced MDSC protected mice against diet-induced metabolic dysfunction and reduced HFD-associated inflammation, but also increased the accumulation of fat, enhanced tumor progression, and spontaneous metastasis and reduced survival time. HFD-induced MDSC facilitated tumor growth by limiting the activation of tumor-reactive CD8+ T cells. Leptin, an adipokine that regulates appetite satiety and is overexpressed in obesity, undergoes crosstalk with MDSC in which leptin drives the accumulation of MDSC while MDSC down-regulate the production of leptin. Collectively, these studies demonstrate that although MDSC protect against some metabolic dysfunction associated with HFD they enhance tumor growth in HFD mice and that leptin is a key regulator linking HFD, chronic inflammation, immune suppression, and tumor progression.
Early events in TNF signaling: a story of associations and dissociations
Authors: Darnay Bryant G , Aggarwal Bharat B 
Published: January 2018

Abstract
At the cellular level, the multifunctional cytokine tumor necrosis factor (TNF) modulates growth and activates genes through various intermediates, including protein kinases, protein phosphatases, reactive oxygen intermediates, phospholipases, proteases, sphingomyelinases, and transcription factors. Unlike many cytokine receptors, however, the cytoplasmic domain (CD) of the TNF receptors lacks an intrinsic protein kinase activity and yet on interaction with ligand it phosphorylates various proteins. Although the kinetics of most of these activities differ, their interactions are coordinated through the selective interplay between the CD of the receptors and the associated proteins. A unique pathway has been identified by the ability of the TNF receptors to associate with a novel family of proteins. Two distinct families of proteins have emerged, the TNF receptor-associated factors (TRAFs) and the death domain homologues. The cloning of members of these gene families and the identification of the protein-interaction motifs found within their gene products has initiated the molecular identity of factors (TRADD, FADD/MORT, RIP, FLICE/ MACH, and TRAFs) associated with both of the p60 and p80 forms of the TNF receptor and with other members of the TNF receptor superfamily. In this review, we summarize these and other TNF receptor-associated proteins and their potential roles in regulating the activation of nuclear factor-κB and apoptosis, two major responses activated by engagement of TNF receptors by the ligand.
Enhanced cytokine production by milk macrophages following infection with respiratory syncytial virus
Authors: Sone Shigemi , Tsutsumi Hiroyuki , Takeuchi Ryoh , Matsuda Kazuko , Lmai Shosuke , Ogra Pearay L , Chiba Shunzo 
Published: January 2018

Abstract
Paired samples of milk and serum collected 3 days postpartum from 20 women were tested for the presence and level of interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ) by enzyme immunoassay. The expression of these cytokine mRNAs in milk macrophages from eight donors were semiquantitatively analyzed by reverse transcriptase-polymerase chain reaction. The effects of respiratory syncytial virus (RSV) infection on cytokine production were determined in five samples of milk macrophages. Over 90% of the milk samples tested exhibited detectable levels of IL-1β, IL-6, and TNF-α. No IL-12 or IFN-γ activity was detected in the milk. IL-6 activity was weakly detected in about 45%, and TNF-α activity in about 10% of the serum samples tested. However, no IL-1β, IL-12, or IFN-γ activity was demonstrated in any of the serum samples. Milk macrophages from eight subjects all exhibited mRNA for IL-1β, TNF-α, and IL-6, and IFN-γ mRNA in six of eight subjects, although no IFN-γ was detected in any of the 20 samples of milk tested. RSV exposure resulted in a 2- to 100-fold increase in the expression of IL-1β, IL-6, and TNF-α mRNA as well as cytokine protein. Although RSV infection enhanced the expression of IFN-γ mRNA, no detectable IFN-γ was produced by the milk macrophages. These observations suggest that the milk macrophages are actively engaged in the physiological production of IL-1β, IL-6, TNF-α, and IFN-γ in the mammary gland and continue to possess the capacity to increase production of these cytokines in response to RSV and possibly other viral infections.
Leukocyte contribution to parenchymal cell death in an experimental model of inflammation
Authors: Tung David K-L , Bjursten Lars M , Zweifach Benjamin W , Schmid-Schönbein Geert W 
Published: January 2018

Abstract
The relationship between leukocyte migration and parenchymal cell death in vivo remains poorly documented. Accordingly, cell killing in the rat mesentery, as recorded by propidium iodide staining, was investigated with an intravital approach. Superfusion of platelet-activating factor (PAF, 10–8 M) or N-formyl-methionyl-leucyl-phenylalanine (fMLP, 10–8 M) led to extensive leukocyte extravasation but no significant cell death. In contrast, pretreatment with 10–8 M PAF or fMLP for 1 h, followed by superfusion of PAF in combination with fMLP (both at 10–8 M) led to an increase in cell death. Mesenteric parenchymal cells but no endothelial cells were killed. Some of the dead cells were identified as granulocytes/monocytes that were already in the tissue at the start of the experiment. The incidence of cell death was lower but not eliminated when leukocyte migration was blocked with a monoclonal antibody against CD18. A xanthine oxidase inhibitor, BOF-4272, failed to diminish cell death, whereas a hydroxyl radical scavenger, dimethylthiourea, attenuated cell killing without an effect on the number of adhering and migrating leukocytes. These observations demonstrate that leukocytes serve as a factor in the killing of extravascular cells only after the development of a level of stimulation that differs from that required to induce a migratory stimulus into the extravascular space.
Porcine bone marrow myeloid cells: phenotype and adhesion molecule expression
Authors: Summerfield Artur , McCullough Kenneth C 
Published: January 2018

Abstract
The purpose of this study was the discrimination of porcine bone marrow hematopoietic cell (BMHC) subpopulations and cell maturation stages by using cluster of differentiation (CD) and Swine Workshop Cluster (SWC) molecules, combined with cell size, granularity, and the capacity to generate an oxidative burst. SWC3 was the earliest myeloid marker identified in the differentiation pathways. Through SWC3/SWC8 double labeling, three populations committed to the myeloid lineage were discriminated: early myeloid progenitors, which were SWC3lowSWC8–; cells committed to the granulocytic lineage, which were SWC3+SWC8+; monocytic cells, which were SWC3+-SWC8–. The SWC3lowSWC8– myeloid progenitors expressed high levels of CD44 and CD49d, but no CD14. Among the SWC3+SWC8+ granulocytic cells, the most immature were CD14– CD11a/18– CD44low, an intermediate stage was CD14+CD11a/18lowCD44–, and the most mature were CD14+CD11a/18high–CD44high. Only the latter could generate a rapid oxidative burst. Moreover, during granulocytic maturation, a constant decrease in CD49d/29 expression was observed. In contrast, the SWC3+SWC8– monocytic cells were mainly CD14+ and expressed high levels of the adhesion molecules. These results define porcine hematopoietic differentiation and maturation stages. Similarities in human and porcine adhesion molecule expression have been identified, suggesting common functionalities in the regulation of hematopoiesis and the potential of the pig as a model for hematopoietic studies.
Activation-associated changes in blood and bone marrow neutrophils
Authors: Klut Maria E , Whalen Beth A , Hogg James C 
Published: January 2018

Abstract
Accelerated granulocytopoiesis and polymorphonuclear leukocyte (PMN) activation via the complement system are important events in the inflammatory response. This study tests the hypothesis that PMN of the peripheral blood and the bone marrow behave differently when stimulated with zymosan-activated plasma (ZAP). PMN were treated with ZAP and processed to determine the content and distribution of F-actin, the expression of CD18 integrins, and the cell area/shape with the use of a combination of flow cytometry, fluorescence, and light microscopy. The results show that untreated bone marrow PMN display similar F-actin content and cell area but express less CD18 than peripheral blood PMN. ZAP-activated peripheral blood PMN show a marked increase in the F-actin content, CD18 expression, cell area, and length. Highly elongated PMN develop a polar shape in which microfilaments are redistributed in cell protrusions and CD18 is located in the uropod and the lamellipodium. In comparision, activated bone marrow PMN show a lower and more transient increase in the F-actin content, express less CD18, show a reduced increase in the cell area, and display reduced polarity and microfilament redistribution. We conclude that bone marrow PMN show lower complement-activation response than peripheral blood PMN and suggest that the lower expression of surface membrane integrins and related cytoskeletal filaments may account for their reduced ability to develop the polar shape required for diapedesis and migration.
Mast cell granules potentiate endotoxin-induced interleukin-6 production by endothelial cells
Authors: Li Yuai , Stechschulte Ann C , Smith Donald D , Lindsley Herbert B , Stechschulte Daniel J , Dileepan Kottarappat N 
Published: January 2018

Abstract
Mast cells are constituent cells of vascular tissue and their numbers are increased in atherosclerotic vessels. To gain insight into the role of mast cells in vascular inflammation, the effect of mast cell granules (MCG) on endothelial cell production of interleukin-6 (IL-6) was examined. Human umbilical vein endothelial cells (HUVEC) were cultured with lipopolysaccharide (LPS) in the presence or absence of rat peritoneal MCG and IL-6 production was assayed by enzymelinked immunosorbent assay. The interaction of MCG with HUVEC in culture was examined by electron microscopy (EM). The EM studies revealed that MCG are internalized by HUVEC and appear intact even after 24 h in culture. Unactivated HUVEC produced little or no IL-6 either in the presence or absence of MCG. Treatment of HUVEC with LPS stimulated IL-6 production in a dose- and time-dependent fashion. Addition of MCG to LPS-activated HUVEC resulted in the potentiation of IL-6 production at all LPS doses. MCG-induced enhancement of IL-6 production was evident even at a mast cell-to-endothelial cell ratio of 1:32. The enhancement of IL-6 production by MCG was also seen when tumor necrosis factor α was used as an activator. Although potentiation was evident when MCG were added 6 h before or after LPS stimulation, the maximum effect was noted when MCG and LPS were added simultaneously. MCG-mediated enhancement of IL-6 production was abrogated by pretreating MCG with protease inhibitors. Although MCG proteases potentiate IL-6 production by HUVEC, they do not degrade secreted IL-6. These results demonstrate that MCG interact with endothelial cells and modulate the production of an important inflammatory cytokine.
Characterization of a culture-derived CD15+CD11b- promyelocytic population from CD34+ peripheral blood cells
Authors: Unverzagt Kristen L , Bender James G , Loudovaris Maureen , Martinson Jeffrey A , Hazelton Bonnie , Weavert Charles 
Published: January 2018

Abstract
Selected CD34+ cells from mobilized apheresis products were cultured in serum-free or serum-containing media supplemented with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and stem cell factor (SCF; c-kit ligand). We examined the emergence of a CD15+ CD11b- population, which appeared morphologically to be promyelocytes. This CD15+CD11b- population can be further expanded in culture into morphologically mature granulocytes. In an attempt to characterize this culture-derived CD15+CD11b- promyelocytic population, single cells were clone sorted into wells of a Terasaki plate containing various growth factors. We compared the growth factor requirements and kinetics of this apheresis culture-derived CD15+ CD11b- population to the CD15+CD11b- population from fresh bone marrow samples. Our studies indicate that the CD15+CD11b- promyelocytic population from bone marrow and blood are equivalent in their ability to proliferate and in their requirements for growth factors. The CD15+CD11b- population in vitro shows a high proliferative capacity when compared with the other CD15/CD11b populations (CD15-CD11b-, CD15+CD11b+, CD15-CD11b+). Thus, we can manipulate CD34+ cells in vitro to proliferate and differentiate toward a mature neutrophil lineage. The CD15+ CDllb- promyelocytic population derived from this culture may represent the most effective cultured cell population for therapeutic reduction of neutropenia in vivo based on both its stage of differentiation and its proliferative potential.
Enhanced mobilization of hematopoietic progenitor cells by mouse MIP-2 and granulocyte colony-stimulating factor in mice
Authors: Wang Jian-bin , Mukaida Naofumi , Zhang Yi , Lto Takaaki , Nakao Shinji , Matsushima Kouji 
Published: January 2018

Abstract
Human interleukin-8 (IL-8) induces a rapid mobilization of hematopoietic progenitor cells (HPCs) into peripheral blood in mice and primates. Because an exact homologue of human IL-8 does not exist in mice, a chemokine, macrophage inflammatory protein-2 (MIP-2), is supposed to substitute the function of IL-8 in mice. Hence, we investigated the capacity of mouse MIP-2 to induce HPC mobilization in mice. Mouse MIP-2 induced, in either untreated or splenectomized mice, a rapid HPC mobilization, as evidenced by increased numbers of colony-forming unit granulocyte-macrophage (CFU-GM) and lineage marker (Lin)- c-kit+Sca-1 + cells. Although release of elastase from activated neutrophils was proposed to be involved in IL-8-induced HPC mobilization, mouse MIP-2 induced similar levels of HPC mobilization in elastase-deficient beige mice at a similar level to normal ones. This HPC mobilization by MIP-2 was markedly enhanced by pretreatment with granulocyte-colony-stimulating factor (G-CSF). Moreover, the combination of G-CSF and MIP-2 apparently down-regulated L-selectin expression on Lin- Sca-1 + cells in peripheral blood as well as bone marrow. Thus, MIP-2 may down-modulate the interaction between HPCs and bone marrow stroma by reducing L-selectin expression on HPCs and cause rapid mobilization of HPCs into peripheral blood.
Suppression of TNF-α gene expression by hemin: implications for the role of iron homeostasis in host inflammatory responses
Authors: Silver Bernard J , Hamilton Beverly D , Toossit Zahra 
Published: January 2018

Abstract
Tumor necrosis factor α (TNF-α) has multiple effects on iron homeostasis and erythropoiesis and has been implicated in the pathogenesis of the anemia of inflammation. We postulated that intracellular iron in turn may regulate the expression of TNF-α. In the human monocytic leukemia cell line, THP-1, low basal TNF-α message levels were stimulated (sevenfold) when serum was excluded from the culture medium. Addition of hemin completely suppressed TNF-α expression. Similarly, hemin suppressed lipopolysaccharide-induced expression of TNF-α. Snprotoporphyrin, an inhibitor of heme oxygenase (which releases iron from hemin), prevented hemin-induced suppression of TNF-α expression. Conversely, the intracellular iron chelator, desferrioxamine, stimulated TNF-α expression. Thus, the expression of TNF-α, itself a physiological regulator of iron homeostasis, appears to be controlled by intracellular levels of iron. J.
The role of CXC chemokines in the regulation of angiogenesis in non-small cell lung cancer
Authors: Arenberg Douglas A , Polverini Peter J , Kunkel Steven L , Shanafelt Armen , Hesselgesser Joseph , Horuk Richard , Strieter Robert M 
Published: January 2018

Abstract
Angiogenesis is a critical component of tumor biology. In recent years newer techniques of cell and molecular biology have led to important advances in our understanding of this process. The regulation of angiogenesis depends on a balance between the activity of local factors that promote (angiogenic factors) or inhibit (angiostatic factors) neovascularization. Nowhere is this paradigm of a balance more apparent than in the study of tumor-associated angiogenesis. Tumors promote angiogenesis through a combination of overexpression of angiogenic factors and local inhibition of angiostatic factors. This strategy leads to an angiogenic environment that promotes tumor growth and metastases. Our laboratory has focused studies on the role of the CXC chemokine family in the regulation of angiogenesis by non-small cell lung cancer (NSCLC). In this article, we review our findings that the CXC chemokine family is composed of members that are either angiogenic or angiostatic. We have found that in NSCLC an imbalance exists in the expression of these factors that favors tumor-derived angiogenesis, and therefore tumor growth and metastases. Furthermore, when this imbalance is corrected to reduce the presence of angiogenic factors or increase the presence of angiostatic factors, tumor growth and metastases are reduced.
Regulation of CCR2 chemokine receptor mRNA stability
Authors: Xu L , Rahimpour R , Ran L , Kong C , Biragyn A , Andrews J , Devries M , Wang J-M , Kelvin D J 
Published: January 2018

Abstract
During inflammatory and immunological responses, leukocytes respond to external stimuli by altering the stability of cytokine and cytokine receptor messages. Change in message stability is an effective mechanism for rapidly regulating steady state levels of mRNA. Cytokine messages containing A-U-rich elements located in the 3′ untranslated region (ARE) are the best studied examples of this process. AREs have been shown to act as targeting motifs for degradation of cytokine and transcription factor messages. We have recently observed that the interleukin-8 (IL-8) receptor messages, IL-8RA and B (CXCR1 and CXCR2), also undergo changes in stability in response to the inflammatory stimulator lipopolysaccharide (LPS). To determine whether regulation of message stability is a common mechanism for modulation of chemokine receptor mRNA we explored whether the stability of the CC chemokine receptor message for CCR2 (monocyte chemotactic protein-1 receptor) is also regulated by LPS. We found that LPS induces a rapid loss of steady state levels of CCR2 message through message degradation. Furthermore, LPS stimulated the decay of Poly(A) CCR2 mRNA faster than total CCR2 RNA, indicating that deadenylation is the first step in LPS-induced CCR2 RNA degradation. We conclude from these experiments that LPS stimulates the rapid degradation of CCR2 messages through a two-step process, deadenylation followed by degradation of the message body. In contrast to the results obtained for CCR2 mRNA, macrophage inflammatory protein-1α messages, which contain an ARE motif, were stabilized by LPS stimulation, indicating that chemokine and chemokine receptor mRNA stability are regulated by different and opposing mechanisms.
The fast signal diffusion limit in a chemotaxis system with strong signal sensitivity
Authors: Mizukami Masaaki 
Published: January 2018

AbstractThis paper gives an insight into making a mathematical bridge between the parabolic‐parabolic signal‐dependent chemotaxis system and its parabolic‐elliptic version. To be more precise, this paper deals with convergence of a solution for the parabolic‐parabolic chemotaxis system with strong signal sensitivity
urn:x-wiley:0025584X:media:mana201700270:mana201700270-math-0001to that for the parabolic‐elliptic chemotaxis system
urn:x-wiley:0025584X:media:mana201700270:mana201700270-math-0002where Ω is a bounded domain in () with smooth boundary, is a constant and χ is a function generalizing
urn:x-wiley:0025584X:media:mana201700270:mana201700270-math-0006In chemotaxis systems parabolic‐elliptic systems often gave some guide to methods and results for parabolic‐parabolic systems. However, the relation between parabolic‐elliptic systems and parabolic‐parabolic systems has not been studied except for the case that . Namely, in the case that Ω is a bounded domain, it still remains to analyze on the following question: Does a solution of the parabolic‐parabolic system converge to that of the parabolic‐elliptic system as ?
This paper gives some positive answer in the chemotaxis system with strong signal sensitivity.