bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional inhibition of endotoxin–induced monokine synthesis following heat shock in murine peritoneal macrophages
Authors: Snyder Yvonne M , Guthrie Laura , Evans Glenn F , Zuckerman Steven H 
Published: January 2018

Abstract
The role of heat shock proteins (HSP) during the inflammatory response has been controversial. The effect of heat shock (HS) on the synthesis of the monokines tumor necrosis factor (TNF) and interleukin 1 (IL-1) by endotoxin–stimulated thioglycollate–elicited peritoneal macrophages was investigated. HS was deemed to have affected macrophages if a 70 kD HSP appeared on SDS gels; identity of this protein as the highly conserved HSP70 was then confirmed by immunoprecipitation. Maximal increases in HSP70 were apparent 2–5 h after HS at 45° for 12 min. Synthesis of HSP70 was no longer detected 24 h post HS. A reciprocal relationship between HSP70 and TNF was apparent in kinetic studies. TNF was not detected in culture supernatants if macrophages were endotoxin–stimulated 2 to 6 h after HS; however, the same stimulation 24 h later induced significant TNF secretion. RNA analysis of HS and non–HS macrophage cultures demonstrated a 60–fold reduction in TNF message in the HS macrophages 1 h after endotoxin stimulation. TNF mRNA levels remained depressed at 6 h while the HSP70 message had increased 30–fold. The ability of HS macrophages to ingest antibody–coated erythrocytes was not significantly affected following heat treatment. Macrophage response to HS can be said to inhibit transcription of inducible monokines while retaining other macrophage functions.
Anti-class II MHC antibody induces multinucleated giant cell formation from peripheral blood monocytes
Authors: Orentas Rimas J , Reinlib Leslie , Hildreth James EK 
Published: January 2018

Abstract
Multinucleated giant cells (MGCs) are an integral part of the host immune response to infectious disease and are seen in granulomas induced by pathogens and inorganic substances. We have developed a novel system for the production and study of MGCs: Peripheral blood monocytes, when cultured in the presence of anti–class II major histocompatibility complex monoclonal antibodies (MHC mAb's) and lymphocyte-conditioned medium form MGCs within 48 h. MGC formation was strictly dependent on the presence of anti–class II MHC mAb's and lymphocyte-conditioned medium. MGC formation was not induced by mAb's to other monocyte surface proteins. None of the previously identified macrophage fusion factors (calcitriol, interleukin 4, interferon-γ) were able to substitute for the lymphocyte-conditioned medium in our assay; however, the conditioned medium could be replaced by the phorbol ester phorbol 12-myristate 13-acetate. We have also demonstrated that the induction of MGCs by anti–class II MHC antibody and phorbol ester requires protein kinase C activity, because MGC formation was totally inhibited by the protein kinase C inhibitors staurosporine and H-7. In analyzing the signal induced by anti–class II MHC mAb's we have demonstrated that cross-linking of the class II MHC antigens with intact mAb's, or with F(ab')2 fragments of anti–class II MHC mAb's and F(ab')2 fragments of rabbit antimouse (RAM) immunoglobulin G, produced an intracellular calcium rise. Furthermore, using the calcium channel blocker verapamil, it was demonstrated that calcium channel activity is necessary for MGC formation. These data support the view that MGC formation is a tightly regulated differentiative pathway of peripheral blood monocytes that is dependent on protein kinase C second messenger systems and involves an inrease in intracellular calcium concentration.
Contribution of interferon γ and membrane-associated interleukin 1 to the resistance to murine typhoid of Ityr mice
Authors: Kita Eiji , Emoto Masashi , Oku Daisuke , Nishikawa Fumiko , Hamuro Akiko , Kamikaidou Noriaki , Kashiba Shuzo 
Published: January 2018

Abstract
Resistance of mice to Salmonella, typhimurium in the early phase of infection is known to be controlled by the expression of chromosome 1 locus Ity. To clarify the mechanism by which the genetically resistant (Ityr) mice can overcome the first phase of salmonellosis, the early response in DBA/2 (Ityr) and BALB/c (Itys) mice was compared after a subcutaneous injection of S. typhimurium. In both strains, the growth of S. typhimurium was controlled in livers and Kupffer cells until day 3, but thereafter the bacteria multiplied rapidly in BALB/c mice. Over the first 2 days nonspecific responses (changes in levels of blood leukocytes, plasma iron, and α1-antitrypsin) were not significantly different between the strains, and the capacity of Kupffer cells isolated from infected mice of both strains to produce interleukin 1 (IL-1) and tumor necrosis factor α (TNF-α) was of the same degree. Thereafter, only DBA/2 Kupffer cells were able to produce membrane-associated IL-1 (ma IL-1) as well as TNF-α. Moreover, only DBA/2 splenocytes were able to produce interferon γ (IFN-γ) upon stimulation with Salmonella antigens, although concanavalin A-stimulated splenocytes of both strains produced the same level of interleukin 2. Furthermore, administration of recombinant murine IFN-γ and DBA/2 Kupffer cells of day 6 to BALB/c mice 3 days after infection resulted in a significant level of protection, whereas neither of these materials alone induced protection. Injection of anti-TNF-α antibodies did not affect the resistance of DBA/2 mice. Thus, these findings suggest that the early resistance of Ityr mice is partly attributable to their capacity to produce IFN-γ and ma IL-1 after infection.
Regulation of pinocytosis in murine macrophages by colony-stimulating factors and other agents
Authors: Knight Kenneth R , Vairo Gino , Hamilton John A 
Published: January 2018

Abstract
Lucifer yellow (LY) accumulation was used to measure macrophage pinocytosis. The hematopoietic growth factors, macrophage colony-stimulating factor (CSF-1), granulocyte-macrophage CSF (GM-CSF), and interleukin 3, and the macrophage activators, lipopolysaccharide and zymosan, all stimulated LY uptake in both murine bone marrow–derived macrophages (BMMs) and resident peritoneal macrophages (RPMs) without affecting LY efflux. The stimulation of pinocytosis in the poorly cycling RPMs and in BMMs by nonmitogens dissociates stimulation of pinocytosis from subsequent DNA synthesis. Regulation of pinocytosis in BMMs appears to be independent of that of urokinase-type plasminogen activator expression. The increases in CSF-mediated BMM pinocytosis were not inhibited by pertussis toxin, by elevations in intracellular cAMP, or by glucocorticoids and were only partially inhibited by inhibitors of Na+/H+ antiport and Na+/K+-ATPase activities. Protein kinase C activation could be involved in regulating BMM pinocytosis because phorbol myristate acetate, oleoylacyglycerol, and exogenously added phospholipase C can all stimulate it. Ca2+ ionophores were inactive, whereas the Na+/H+ ionophore monensin potently inhibited BMM pinocytosis.
Ontogenetic development, differentiation, and phenotypic expression of macrophages in fetal rat lungs
Authors: Higashi Kenji , Naito Makoto , Takeya Motohiro , Ando Masayuki , Araki Shukuro , Takahashi Kiyoshi 
Published: January 2018

Abstract
Development, differentiation, and distribution of macrophages in fetal rat lungs were investigated immunohistochemically using anti-rat macrophage monoclonal antibodies. In the lung buds, RM-1+ macrophages were first detected on fetal day 13, and some showed reactivity for TRPM-2. They populated in the peribronchial mesenchyme of the lung buds, proliferated in loco, and showed no peroxidase activity in any intracellular organelles. Their immunophenotypic and ultrastructural features were consistent with those of primitive/fetal macrophages. By fetal day 16, some of them expressed ED1, but ED1+ cells were a minor subpopulation throughout the fetal period. On fetal day 18, ED2+ macrophages developed; some also were positive for RM-1, but the others were negative. Both the RM-1+ and ED2+ macrophages were major macrophage subpopulations and expressed Ki-M2R and/or TRPM-3; ED2+ and/or Ki-M2R+ cells are regarded as pulmonary interstitial resident macrophages. In organ culture, a similar expression of differentiation antigens by macrophages was confirmed. None of these macrophages cytochemically showed any peroxidase activity in vivo or in vitro. In the fetal stage, both RM-1+ and ED2+ macrophage subpopulations showed proliferative potential, suggesting their ability to proliferate and survive in vivo.
Platelet activating factor enhancement of lipopolysaccharide-induced tissue factor activity in monocytes: requirement of platelets and granulocytes
Authors: østerud Bjarne 
Published: January 2018

Abstract
Incubation of platelet activating factor (PAF) with heparinized blood caused no induction of tissue factor activity in monocytes. However, when PAF was added in addition to weak lipopolysaccharide (LPS), it amplified the LPS effect by 80%. By using separated fresh cell populations resuspended in plasma, PAF was shown to have no enhancing effect when added to mononuclear cells incubated with platelet-rich plasma in the presence of LPS. In contrast, when granulocytes also were included, PAF caused an almost 3-fold increase in LPS-induced tissue factor activity. A PAF antagonist blocked this effect and also reduced LPS-induced tissue factor activity of monocytes in whole blood in a dose-dependent manner. In the recombined cell incubation system, the maximal inhibition by the antagonist was observed in the presence of granulocytes. These data provide evidence for an effect of PAF on granulocytes that probably generates a product that, together with platelets, enhances LPS-induced tissue factor activity in monocytes.
Flow cytometric analysis of nitric oxide production in human neutrophils using dichlorofluorescein diacetate in the presence of a calmodulin inhibitor
Authors: Krishna Rao K Murali , Padmanabhan Jaya , Kilby Diana L , Cohen Harvey J , Currie Mark S , Weinberg J Brice 
Published: January 2018

Abstract
Dichlorofluorescein (DCFH) oxidation assay measures hydrogen peroxide (H2O2), which is a derivative of superoxide anion. We found that a calmodulin antagonist, W-13, which is known to inhibit superoxide anion generation enhanced the capacity of human neutrophils to oxidize DCFH. To investigate this discrepancy we studied the role of nitric oxide (NO) in DCFH oxidation. Pure NO was capable of oxidizing DCFH, and the product formed had spectral properties identical to oxidized DCFH produced by H2O2. The arginine analog, NG-monomethyl-l-arginine (NMMA), which inhibits NO production, in combination with W-13 completely inhibited the stimulus-induced increase in DCFH oxidation. We conclude that the oxidation of DCFH in human neutrophils can occur by either H2O2 or NO.
Isolation and characterization of four CSF-1-dependent placental macrophage cell lines
Authors: Boocock CA , Hayes M , Chang M-d Y , Pollard JW 
Published: January 2018

Abstract
By selection and cloning in the presence of colony-stimulating factor 1 (CSF-1), we have obtained from separate explants of individual 12- or 13-day mouse placentas four clonal cell lines dependent on CSF-1 for survival and growth in culture. All four cell lines show characteristics consistent with their derivation from placental macrophages. We describe the effects of CSF-1 on growth, morphology, and CSF-1 receptor phosphorylation. One cell line, JPL2A, which shows relatively complete growth arrest in the absence of CSF-1, was characterized in detail with respect to the effects of CSF-1 on DNA synthesis and protein turnover and its response to the duration of CSF-1 stimulation. In contrast to previous studies, our results suggest that extended stimulation leads to continuous recruitment of cells competent to reenter the cell cycle. These findings are discussed in terms of growth factor effects on the cell cycle and the usefulness of these cell lines for further study of growth factor signal transduction in macrophages.
Characterization and identification of interleukin 1 receptors on bovine neutrophils
Authors: Lederer James A , Czuprynski Charles J 
Published: January 2018

Abstract
Interleukin 1 (IL-1) has been shown to modulate various functional activities of neutrophils, presumably by first binding to cell surface IL-1 receptors. In this study, we characterized and identified IL-1 receptors on bovine neutrophils using direct and competitive receptor binding studies and affinity cross-linking analysis. The results of direct binding studies demonstrated that bovine neutrophils bound 125I-labeled bovine IL-1 by a single affinity binding site (Kd = 4.6 nM, 5600 binding sites per cell). Competitive receptor binding studies demonstrated that unlabeled recombinant bovine IL-1β, murine IL-1α, and human IL-1β competitively blocked neutrophil binding of 125I-labeled bovine IL-1β. In contrast, the IL-1 receptor antagonist (IL-1ra) demonstrated no detectable binding to bovine neutrophils as judged by direct and competitive receptor binding assays. Affinity cross-linking of 125I-labeled bovine IL-1β to neutrophils was used to identify cell surface IL-1 receptors. Two specific cross-linked products were observed with molecular sizes of 89 kd (a deduced receptor size of 71.5 kd) and more than 200 kd. The latter may indicate a complex of IL-1 receptor-associated signal-transducing components, IL-1 receptors, and IL-1. The presence of 100 nM unlabeled bovine, murine, or human IL-1 during the receptor binding and cross-linking reactions prevented the formation of cross-linked complexes of 125I-labeled bovine IL-1β and its receptor. In contrast, the IL-1ra failed to inhibit the formation of cross-linked complexes of 125I-labeled bovine IL-1β and its receptor.
Inhibition of neutrophil chemotaxis and activation following decentralization of the superior cervical ganglia
Authors: Carter Lisa , Ferrari J Kent , Davison Joseph S , Befus Dean 
Published: January 2018

Abstract
Recent studies have shown that bilateral decentralization (sympathectomy) of the superior cervical ganglia (SCG) of rats sensitized to the parasite Nippostrongylus brasiliensis attenuated the development of pulmonary inflammation following allergen challenge. Sympathectomy inhibited total leukocyte infiltration into lung lavage fluids, particularly neutrophil infiltration. To define the effects of decentralization of the SCG on neutrophil responses, peripheral blood neutrophils of rats were isolated and tested in in vitro chemotaxis and phagocytosis assays. Neutrophils from rats that were sympathectomized 7 days previously displayed a marked reduction in chemotaxis to N-formyl-methionyl-leucyl-phenylalanine and leukotriene B4 compared to neutrophils from sham-operated or unoperated groups. Although the degree of chemotaxis was greater in blood neutrophils from parasite-infected rats than from uninfected rats, sympathectomy markedly reduced the chemotactic responses of both groups. In addition, neutrophils of sympathectomized rats were unresponsive to lipopolysaccharide-induced metabolic activation as assessed by in vitro phagocytosis and oxidative reduction of nitroblue tetrazolium. Thus, decentralization of the SCG of rats affects the chemotactic responses and functions of neutrophils. Understanding the role of the sympathetic nervous system in modulating the behavior of neutrophils will shed light on the interactions between the nervous and immune systems.
Soybean agglutinin–positive natural suppressor cells in mouse bone marrow inhibit interleukin 2 production and utilization in mixed lymphocyte reactions
Authors: Hoskin D W , Bowser D A , Brooks-Kaiser J C 
Published: January 2018

Abstract
Although natural suppressor (NS) cells resident in bone marrow (BM) have been the subject of intensive study, the exact nature and mode of action of these potentially important immunoregulatory cells are still uncertain. Here we show that NS cells with potent inhibitory effects on mixed lymphocyte reactions (MLRs) can be isolated from BM of normal adult mice by agglutination with the plant lectin soybean agglutinin (SBA). Complement-dependent lysis of SBA receptor–bearing BM cells with antibodies to asialoGM1, Mac-1, Thy-1.2, J11d.2, and 2C1 phenotypic markers reveals the presence of at least two distinct populations of BM NS cells. Most of the SBA-binding BM cells with NS capacity have the null phenotype and resemble hematopoietic stem cells, and some inhibitory SBA+ BM cells express the 2C1 marker found on pregnancy-associated splenic NS cells and the J11d.2 antigen characteristic of B cells and immature T cells. Results of positive selection experiments confirmed these findings. The mechanism of natural suppression was also studied. Evidence is presented that SBA+ BM cells exert NS activity in MLRs by interfering with the production and utilization of interleukin 2. Indomethacin does not relieve natural suppression associated with SBA+ BM cells, indicating that prostaglandin synthesis is not a requirement for inhibitory function. However, neutralizing antibodies to transforming growth factor β (TGF-β) partially reverse the suppression mediated by SBA4 BM cells, suggesting that some BM NS cells may act through the release of an immunosuppressive molecule related to TGFβ.
Subcellular localization of CD66, CD67, and NCA in human neutrophils
Authors: Ducker Thomas P , Skubitz Keith M 
Published: January 2018

Abstract
CD66 and CD67 are granulocyte-specific activation antigens; their surface expression is up-regulated when neutrophils are activated. CD66 antibodies recognize an ~180-kd neutrophil surface protein that is also recognized by anti–carcinoembryonic antigen (CEA) antibodies and is therefore a nonspecific cross-reacting antigen (NCA). CD67 antibodies recognize an ~100-kd neutrophil surface protein that is attached to the membrane via a glycosyl-phosphatidylinositol anchor. To identify an intracellular pool from which CD66 and CD67 could be up-regulated, the subcellular distribution of proteins recognized by CD66 and CD67 monoclonal antibodies and polyclonal anti-CEA was studied. Neutrophil plasma membranes, granules, and cytoplasm were prepared by nitrogen cavitation and differential centrifugation and then analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Most of the 180-kd protein recognized by CD66 antibodies and the 100-kd protein recognized by CD67 antibodies were located in the secondary granule fraction, with lesser amounts detectable in the plasma membrane fraction. Several NCA species ranging from ~40 to 200 kd were identified, and the distribution of these NCAs was different in the primary granules, secondary granules, and plasma membrane fractions. The major NCAs in the plasma membrane fraction were of ~95 to 100 and ~180 to 200 kd; the secondary granule fraction contained major NCAs of ~42, 85, 95 to 100, and 180 to 200 kd. NCAs were also detected in the primary granule fraction, the most prominent being of ~90–100 kd; no NCA of ~180 to 200 kd was detected in the primary granules. The presence of CD66, CD67, and NCAs in the secondary granules suggests secondary granules as a likely source from which these antigens could be recruited to the cell surface with activation. The potential role for NCAs in the primary granules is unknown.
Taxol, a microtubule-stabilizing antineoplastic agent, induces expression of tumor necrosis factor α and interleukin-1 in macrophages
Authors: Bogdan Christian , Ding Aihao 
Published: January 2018

Abstract
Taxol, a naturally occurring diterpene with antitumor activity, induces tubulin polymerization to generate abnormally stable and nonfunctional microtubules. Previously, we showed that taxol has lipopolysaccharide (LPS)-like effects on macrophages. As LPS is a potent inducer of macrophage cytokine production, we investigated whether a similar effect is exerted by taxol. In a dose-dependent manner, LPS-free taxol induced release of biologically active tumor necrosis factor α (TNF) by inflammatory murine macrophages. Taxolinduced production of TNF was inhibitable by interleukin-10. By Northern blot, taxol (10 and 1μM) induced TNF mRNA expression to an extent similar to LPS. Induction of TNF mRNA by 10 μM taxol was detectable at 45 min of stimulation, maximal at 90 min, and evident for at least 8 h. The same low concentration of taxol also induced interleukin 1 (IL-1) α and β mRNA expression. We conclude that taxol triggers macrophages for TNF and IL-1 production. These LPS-like effects of taxol might contribute to its antitumor activity.
Inhibitory role of interleukin-6 in macrophage proliferation
Authors: Riedy MC , Stewart CC 
Published: January 2018

Abstract
We have shown that there are two forms of progenitor cells for macrophages. The first is characterized by a short lag period (about 1 day) before initiating the cell cycle, forms large colonies, is found in the bone marrow, and is in the nonadherent fraction. The second progenitor cell, found primarily in the adherent cell fraction of bone marrow and in peripheral tissues, forms small colonies after 14 days. We investigated the effect of combining interleukin-6 (IL-6) with colony-stimulating factor 1 (CSF-I) on macrophage proliferation. We found that IL-6 inhibited the proliferation of both types of progenitor cells, as well as more differentiated macrophages. This inhibitory effect was reversible because macrophages could initiate a proliferative response after removal of IL-6 from the culture medium. The introduction of anti–IL-6 into macrophage cultures containing IL-6 allowed proliferation, indicating that the effect was IL-6 specific. These results suggest that IL-6 may play a regulatory role in vivo by suppressing the production of bone marrow and tissue macrophages.
Specific ligation of surface α-D-galactosyl epitopes markedly affects the quantity of four major proteins secreted by macrophages
Authors: Warfel Alwin H , Zucker-Franklin Dorothea 
Published: January 2018

Abstract
Activated macrophages (Mφs) have terminal α-D-galactosyl (αD-Gal) residues on their membranes that are not apparent on resting cells. Ligation of these epitopes with Griffonia simplicifolia I-B4 (GSI-B4), a lectin that has specificity for α-D-Gal residues, alters selected Mφ functions. To explore the mechanism(s) that may be responsible for some of the functional changes, alterations in the secretory pattern of [35S]methionine-labeled proteins were assessed when cells were cultured with or without this ligand. The proteins were identified by Western blots and quantitated. Interestingly, α-D-Gal ligation proved to decrease the secretion of some proteins while increasing the secretion of others. Some of the most significant changes were observed in four proteins: fibronectin and transglutaminase were down-regulated by 55 and 66% respectively, while plasminogen activator inhibitor type 2 was increased by 259% and collagenase was increased 1000-fold. These observations show that the emergence of new oligosaccharide epitopes, such as α-D-Gal, concomitant with Mφ activation may serve to mediate the transduction of signals that cause quantitative changes in the elaboration of diverse Mφ products. The biologic significance of the four identified proteins has been well established. Fluctuations in their levels are likely to play a role at sites of chronic inflammation.