bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Expression of M-CSF, G-CSF, and GM-CSF by Human Monocytes
Authors: Lee Mei-Ting , Kaushansky Kenneth , Ralph Peter , Ladner Martha B 
Published: January 2018

Abstract
The colony-stimulating factors (CSF) belong to a group of proteins which regulate blood cell production. Human monocytes allowed to adhere express high levels of M-CSF transcripts and secreted protein at 24 h in the presence but not in the absence of indomethacin (Indo), an inhibitor of prostaglandin E (PGE) production. When induced with lipopolysaccharide (LPS), adherent monocytes express M-CSF, G-CSF, and GM-CSF transcripts and secrete these proteins and TNF. M-CSF and GM-CSF messages increase in LPS-induced monocytes by the addition of Indo, while G-CSF mRNA appears to decrease. Exogenous addition of PGE-2 to LPS-induced monocytes down-modulates the expression of M-CSF and GM-CSF transcripts. G-CSF message is elevated, suggesting an alternate pathway to G-CSF regulation. PGE-2 inhibits the secretion of CSFs and TNF. In contrast, LPS-induced monocytes held 24 h in nonadherent culture express G- and GM-CSF but not M-CSF. Monocytes that are adhered for 24 h and then treated with LPS for an additional 24 h express only M-CSF message and secrete M-CSF and TNF. PGE-2 added with LPS during the 24–48 h induction blocks M-CSF and TNF production, but appears to enhance M-CSF message expression, in contrast to its effect on 0 h inductions. These results suggest that adherence alone induces M-CSF gene expression, but low levels of PGE or other arachidonic acid metabolites limit this expression. Other events in 1 d-cultured monocytes block the ability to induce G-CSF and GM-CSF expression with LPS, and block the suppressive effect of PGE-2 on M-CSF expression at the RNA level.
Adenosine and Its Derivatives Control Human Monocyte Differentiation Into Highly Accessory Cells Versus Macrophages
Authors: Najar Hossain Motieian , Ruhl Stephan , Bru-Capdeville Anne Christine , Peters Johann Hinrich 
Published: January 2018

Abstract
Human peripheral blood monocytes have been found to undergo a transitory state of high accessory activity before they fully become macrophages. Time kinetics were done to follow this accessory potential. Studying the regulation of accessory activity, we have found that monocyte-derived accessory cells (m-AC) pass through two phases of development, which both are adversely controlled by cyclic nucleotides. Phase I is positively correlated by intracellular cAMP increase and can be arrested by adenosine 3′;5′ cyclic monophosphate (cAMP) and synergystic agents. In addition to cAMP, non-cyclic adenine nucleotides and adenosine also mimic all cAMP effects. This behavior is explained by the known presence of surface 5′ nucleotidase and adenosine receptor, which in turn leads to activation of adenylate cyclase. At phase II serum is required to convert m-AC into macrophages. In the absence of serum, cells were arrested in the m-AC state. Adenine nucleotides effectively counteract the serum induction leading to the development of m-AC even in the presence of serum. Monocyte/macrophage markers such as Fc receptors and non-specific esterase strictly correlate negatively with the expression of accessory activity. Morphologically, the appearance of veils positively correlates with all experimental situations of high accessory activity. Therefore, it is evident that serum contains regulatory factors that strongly modify the accessory potency of the m-AC via the cyclic nucleotide system, thus presenting a potent immunoregulatory principle at the beginning of the immune cascade.
Recombinant Granulocyte–Macrophage Colony-Stimulating Factor Activates Human Macrophages to Inhibit Growth or Kill Mycobacterium avium Complex
Authors: Bermudez Luiz Eduardo M , Young Lowell S 
Published: January 2018

Abstract
Organisms belonging to the Mycobacterium avium complex (MAC) are associated with life-threatening bacteremia in patients with the acquired immunodeficiency syndrome (AIDS). As these organisms survive within macrophages, we examined the ability of recombinant human granulocyte–monocyte colony-stimulating factor (GM-CSF) to activate human monocyte-derived macrophages to inhibit the intracellular growth or kill the most mouse-virulent MAC strain In our collection that belongs to serotype 1. While unstimulated cells did not inhibit intracellular growth of MAC, macrophages activated by GM-CSF (10–104 U/ml) inhibited or killed up to 58 ± 5% of the initial inoculum. This activation was dose-dependent, with maximal change occurring with a dose of 100 U/ml after 72 hr exposure. Inhibition or killing was demonstrated if GM-CSF was given both before or after establishment of infection. The combination of GM-CSF (102 U/ml) plus TNF (102 U/ml) augmented macrophage killing (range, 31 ± 4%) compared with GM-CSF (102 U/ml) alone, but the combination of recombinant human interferon-gamma (IFNγ) plus GM-CSF resulted in a significant decrease in intracellular inhibition of growth or killing (13.3 ± 2%) compared with 57.7 ± 5% obtained with GM-CSF alone. These results indicate that: 1) GM-CSF can activate macrophages to inhibit intracellular growth or kill MAC; 2) killing may be augmented by TNF; and 3) IFNγ may impair GM-CSF-dependent macrophage activation.
Characteristics of the Chemotactic Activity of Heparin Cofactor II Proteolysis Products
Authors: Hoffman Maureane , Pratt Charlotte W , Corbin Lisa W , Church Frank C 
Published: January 2018

Abstract
The physiological function of the serpin (serine proteinase inhibitor) heparin cofactor II (HCII) is not well understood. A role for HCII as an inhibitor of thrombin in the presence of dermatan sulfate and heparin has been proposed. Neutrophils (PMN) are the major cellular component of acute inflammation. HCII can be proteolytically inactivated by cathepsin G (CG) and elastase (LE), which are released by stimulated PMN. We have recently shown that reaction products of HCII with CG and LE are potent chemotaxins for PMN. Monocytes (monos) appear later in the course of inflammation than do PMN. They differentiate into macrophages in the tissues and participate in healing of damaged tissue and initiating immune responses. We found that the proteolysis products of HCII were chemotactic for monocytes in a fashion similar to their effects on PMN. At 10-8 to 10-9 M, the chemotactic activity of HCII proteolysis products was comparable to that of 10-8 M N-formyl-Met-Leu-Phe (fMLP). The chemotactic activity of HCII-proteinase reaction products is mediated by a different mechanism than that of α1 proteinase inhibitor (α1PI)-LE complexes or fMLP. Our data suggest that chemotactic activity generated by proteolysis of HCII is not due to the conformational change induced by cleavage of the exposed loop near the reactive site nor by release of the reactive site peptide. We also compared the effects of HCII reaction products and fMLP on expression of Mac-1 and p150,95 adhesive proteins. Mac-1 has been implicated in mono adhesion and chemotaxis and as a potential initiator of coagulation. The surface expression of Mac-1 was not increased above control levels by incubation of leukocytes with HCII digests, even though fMLP did increase surface Mac-1. Proteolysis products of HCII could play a role in the initial influx of PMN into a thrombus, and in the transition from acute to chronic inflammation, or to granulation and healing.
Eicosanoid Production in Nonparenchymal Liver Cells Isolated From Rats Infused With E. coli Endotoxin
Authors: de Turco E B Rodriguez , Spitzer J A 
Published: January 2018

Abstract
Continuous i.v. infusion of a nonlethal dose of Escherichia coll endotoxin induced an early (3-h) accumulation of neutrophils in the rat liver followed by a later (30-h) greater extravasation of mononuclear phagocytes (MNP). These inflammatory cells, recovered together by centrifugal elutriation, were analyzed for their potential capacity to metabolize [1-14C]-AA. Ca2+ ionophore A23187 (5 μM) stimulated the release of [1-14C]-AA from PC and PI both in cells from saline- and ET-infused rats, the latter showing a higher capacity to further metabolize AA to eicosanoids. LTB4 and 5-HETE were the major metabolites accumulated in cells from rats infused with ET for 3 h, while PGD2 played the main role in cells from saline-infused rats. This could reflect [1-14C]-AA metabolism by PMNP and Kupffer cells, respectively. By 30 h of ET-infusion, a shift from PGD2 to PGE2 release was observed. These results suggest that eicosanoids released by nonparenchymal cells (i.e., Kupffer and endothelial cells) and PMNP in the liver of ET-infused rats may alter the normal intercellular information flow between parenchymal and nonparenchymal cells, contributing to the severe impairment in liver function and metabolism during endotoxicosis and sepsis.
Oxidative Metabolism of Polymorphonuclear Leukocytes: Modulation by Adhesive Stimuli
Authors: Laurent F , Benoliel A M , Capo C , Bongrand P 
Published: January 2018

Abstract
Different agents such as phorbol myristate acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe), or opsonized zymosan induced an oxidative burst in rat peritoneal polymorphonuclear leukocytes (PMNs) elicited by casein. Plastic adhesion of PMNs down-regulated superoxide (O2) release stimulated by PMA or fMet-Leu-Phe but had no effect on zymosan-induced O2 generation, indicating that the O2 forming enzyme, the NADPH oxidase, was not affected by modulation and that a common step of the transductional events induced by PMA or fMet-Leu-Phe might be involved in this regulation. We demonstrated that a differential translocation of protein kinase C (PKC) was not responsible for that modulation. PMA-induced secretion of granule content (vitamin B12-binding protein) was not susceptible to modulation, suggesting that the transductional pathways leading to O2 generation and granule secretion are partly separated. The adhesion of PMNs to different substrates (glass, plastic, albumin-, laminin-, fibronectin-, poly-lysine-, or concanavalin A-coated plastic) down-regulated to different extent superoxide release. Whether the nature of the biochemical signal induced by the diverse adhesive stimuli or a physical parameter such as binding strength was involved in this differential behavior remains to be elucidated. Since adhesiveness was dependent on the state of the cytoskeleton and O2 inducers were reported to stimulate actin polymerization, we studied the F-actin content and distribution of PMNs by using the specific fluorescent probe NBD-phallacidin and an original methodology allowing a quantitative analysis of fluorescence on both adherent and suspended cells. PMA induced a polarization of F-actin on suspended PMNs but had no effect on the intracellular distribution of F-actin in adherent PMNs. Thus, we suggest that the adhesion of PMNs induced an immobilization of F-actin, possibly correlated to the down-regulation of one of the transductional pathways involved in the NADPH oxidase activation.
Tumor Necrosis Factor and Granulocyte Macrophage-Colony Stimulating Factor Stimulate Human Macrophages to Restrict Growth of Virulent Mycobacterium avium and to Kill Avirulent M. avium: Killing Effector Mechanism Depends on the Generation of Reactive Nitrogen Intermediates
Authors: Denis Michel 
Published: January 2018

Abstract
An avirulent and a virulent strain of Mycobacterium avium were selected on the basis of their growth patterns in human monocyte-derived macrophages. The virulent 7497 M. avium grew progressively in untreated macrophages, whereas the avirulent LR/149 M. avium was killed to a moderate extent by untreated human macrophages (50% of the original infectious inoculum killed 7 days after infection). We set out to investigate the possibility of modulating these growth patterns by cytokine treatment. Application of tumor necrosis factor (TNF) (100 U/ml) led to macrophages restricting significantly the growth of virulent M. avium 7497 (tenfold decrease at 7 days). TNF was also effective at modulating positively the interaction between avirulent LR/149 M. avium and macrophages inasmuch as TNF-treated cells killed 99% of infecting mycobacteria at 7 days. Granulocyte macrophage-colony stimulating factor (GM-CSF) (100–10,000 U/ml) treatment led to macrophages being as mycobacteriostatic for virulent 7497 M. avium as TNF-α-treated cells (i.e., tenfold reduction in growth). Treatment of macrophages with both GM-CSF and TNF-α was shown to have additive effects on bacteriostatic activity on M. avium. The mechanism of killing of avirulent M. avium by TNF-α was shown to be dependent on the generation of reactive nitrogen intermediates, as seen by inhibition of effector mechanisms by NG-monomethyl-arginine and arginase. Moreover, there was a correlation between NO2– generation and mycobactericidal activity of macrophages. Addition of superoxide dismutase reversed the killing of avirulent M. avium by untreated or TNF-treated macrophages. This abrogation was also apparent in chronic granulomatous disease (CGD) macrophages, which were inefficient at generating reactive oxygen intermediates. Moreover, macrophages from CGD patients killed avirulent M. avium as efficiently as cells from normal individuals. We conclude from these results that 1) GM-CSF and TNF-α, alone or in combination, increase effector functions of macrophages against virulent and avirulent strains of M. avium; 2) reactive nitrogen intermediates seem to be involved in this effector mechanism; and 3) superoxide dismutase protected M. avium against macrophage effector function, seemingly by protecting the bacteria against endogenous superoxide anion. The implications of these findings for host resistance to atypical mycobacteria are discussed.
Cellular Binding Mechanism on Rat Macrophages for Sialylated Glycoconjugates, Inhibited by the Monoclonal Antibody ED3
Authors: Damoiseaux J G M C , Döpp E A , Dijkstra C D 
Published: January 2018

Abstract
The mAb ED3 recognizes a subpopulation of rat macrophages, with a highly restricted tissue distribution. The tissue distribution as well as the in vitro expression of the ED3 antigen and of the sheep erythrocyte receptor (SER), binding unopsonized erythrocytes in the mouse, are very similar. This receptor has almost the same binding characteristics, although a different tissue distribution, as the sialic acid binding receptor (SAR), binding ganglioside-coated erythrocytes in the rat In this study we summarize the available literature concerning these sialic acid binding receptors (SER and SAR). Furthermore we have identified ED3 as SER by inhibition studies of erythrocyte binding with mAb ED3, as well as by the newly developed equivalents ED16 and ED17. We also show that light trypsin treatment of alveolar macrophages, expressing SAR, results in SER-like activity. This obtained SER-like activity could not be blocked by the mAb ED3, indicating that SER and SAR are different receptors. It appears that rat macrophages can express two receptors for sialylated glycoconjugates, a high-affinity receptor SER, recognized by mAb ED3, and a low-affinity receptor SAR, not recognized by mAb ED3.
The Human Monocyte-Like Cell Line THP-1 Expresses FcγRI and FCγRII
Authors: Fleit Howard B , Kobasiuk Catherine D 
Published: January 2018

Abstract
THP-1 cells are a monocyte-like cell line derived from a patient with acute monocytic leukemia and unlike other leukemic cell lines has a normal diploid karyotype. We have characterized FcγR expression on this cell line by flow cytometry, radiolabeled lgG1 and monoclonal antibody (mAb) binding assays, and biochemical analysis. Flow cytometric analysis of THP-1 cells with anti-FcγRI, II, and III mAb, and a rabbit anti-FcγRIII F(ab')2 demonstrated that only FcγRI and FCγRII are expressed by these cells. A panel of anti-FcγRIII mAb (anti-CD16) failed to bind to THP-1 cells. Biochemical studies identified polypeptides of 64 to 78 kDa (FcγRI) and of 42 to 53 kDa (FcγRII). FcγR expression was determined by binding of radioiodinated human lgG1 (to detect FcγRI), mAb IV.3 (to detect FcγRII), or rabbit IgG immune complexes. Thirty-five thousand high affinity binding sites (dissociation constant [KD] = 4.22 × 10-9M) for lgG1 were found on THP-1 cells. Interferon-γ (IFNγ) upregulated FcγRI expression by THP-1 cells 2.8-fold, whereas FcγRI on U937 cells was increased six- to eight-fold by this cytokine. Phorbol myristate acetate (PMA), tumor necrosis factor-α (TNFα), and vitamin D3 had no effect on lgG1 binding by THP-1 cells. Fifty thousand IgG molecules in immune complexes bound to THP-1 cells. IFNγ treatment increased this binding by four-fold, PMA treatment resulted in a 50% increase in the number of IgG immune complexes bound, whereas vitamin D3 treated THP-1 cells bound half as many IgG immune complexes as control cells. Binding assays utilizing mAb IV.3 identified 50,000 sites per cell. Treatment of THP-1 cells with IFNγ, TNFα, PMA, or vitamin D3 had no effect on FcγRII expression. That FcγRI plays a predominant role in immune complex binding was demonstrated by inhibition studies. Human lgG1 as well as mouse lgG2a mAb to FcγRII inhibited immune complex binding by 76 to 84%, whereas mouse lgG1 mAb to FcγRII had minimal effect on immune complex binding. FcγR expression may not be linked to differentiation of THP-1 cells since only 1,25 vitamin D3 was able to induce the expression of CD14, a marker of mature monocytic phenotype.
Effect of Dietary Fish Oil on Development and Selected Functions of Murine Inflammatory Macrophages
Authors: Hubbard Neil E , Somers Scott D , Erickson Kent L 
Published: January 2018

Abstract
Inflammatory macrophages from mice fed diets containing menhaden fish oil (MFO) have a reduced capacity for cytotoxicity of mastocytoma cells upon activation with interferon-γ (IFNγ) and lipopolysaccharide due to an altered responsiveness to IFNγ. In an effort to elucidate further how dietary MFO effects macrophage function, we have studied the maturation of inflammatory macrophages from mice fed MFO compared with mice fed safflower oil (SFO) using several processes that serve as markers of the activational state. No significant differences in the recruitment or percentage of peritoneal exudate cells as macrophages after thioglycollate injection and no differences in spreading, binding, or phagocytosis of sheep erythrocytes or phagocytosis of yeast by inflammatory macrophages were observed when the dietary groups were compared. However, MFO macrophages had an altered capacity for peroxide release when stimulated with unopsonized zymosan (10–200 μg/ml). Furthermore, to elucidate how MFO feeding could alter IFNγ-induced responses of inflammatory macrophages, we assessed phorbol-12-myristate-13-acetate-induced hydrogen peroxide production and expression of class II MHC determinants (la). There were no differences between macrophages from mice fed the two diets with respect to the production of peroxide when they were preincubated with 0.1–10 U/ml of IFNγ. However, MFO macrophages had greater peroxide production after enhancement with 100 U/ml of IFNγ. With respect to la induction, the percentage of macrophages responding to IFNγ was not altered by diet, and there were no differences in expression of la induced by 24 hr exposure to IFNγ. Thus the differential effect of MFO compared with SFO is probably mediated not by an alteration in the maturation of inflammatory macrophages but rather through the alteration of IFNγ-induced functions such as peroxide production.
Activated Macrophage Conditioned Medium: Identification of the Soluble Factors Inducing Cytotoxicity and the L-Arginine Dependent Effector Mechanism
Authors: Amber Ina J , Hibbs John B , Parker Charles J , Johnson Barbara B , Taintor Read R , Vavrin Zdenek 
Published: January 2018

Abstract
Conditioned medium (CM) from cultures of cytotoxic activated macrophages causes inhibition of mitochondrial respiration, DNA synthesis, and aconitase activity in murine EMT-6 mammary adenocarcinoma cells by an l-arginine dependent effector mechanism. CM induces cytotoxicity and nitrite synthesis in EMT-6 cells in a dose dependent manner. We have identified the soluble factors in CM that induce cytotoxicity and synthesis of inorganic nitrogen oxides from l-arginine by EMT-6 cells. Using functional inhibition experiments, the activity of lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) in CM was investigated. The LPS inhibitor polymyxin B and TNFα antibody produced a modest decrease in nitrite production, while IFNγ antibody markedly inhibited both nitrite production and cytostasis. Simultaneous treatment with polymyxin B, TNFα antibody, and IFNγ antibody reduced EMT-6 cell nitrite production by 81%, and cytostasis by 74%. By Western blot, IFNγ and TNFα were shown to be present in CM. When CM was subjected to hydrophobic interaction chromatography, a single peak of activity was eluted, and Western blot showed that the active fractions contained IFNγ. Furthermore, IFNγ antibody neutralized the activity in these chromatographic fractions. We conclude that induction of inorganic nitrogen oxide synthesis from l-arginine by the synergistic combination of IFNγ, TNFα, and LPS accounts for most of the biologic activity of CM, and that IFNγ is the major priming factor.
Developmental Regulation of the Cytokine Repertoire in Human Macrophages: IL-1, IL-6, TNF-α, and M-CSF
Authors: Scheibenbogen Carmen , Andreesen Reinhard 
Published: January 2018

Abstract
We were interested in the dependence of constitutive and stimulated cytokine secretion on the stage of macrophage (MAC) differentiation in vitro. Elutriation-purified blood MO were cultured up to 28 days and their secretory repertoire was analyzed under adherence conditions at various culture stages. For each of the cytokines tested, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and macrophage colony-stimulating factor (M-CSF), a different pattern of regulation was observed. During the initial phase of maturation (up to day 7 in culture) within which the characteristics of normal MO to MAC transformation are achieved, M-CSF was the only cytokine to be secreted constitutively. From the LPS-dependent cytokines, IL-1β and IL-6 were downregulated whereas TNF-α levels increased severalfold. For the release of IL-1β, IL-6, and TNF-α a synergistic effect of interferon-gamma (IFN-g) and lipopolysaccharide (LPS) was observed. M-CSF release increased until day 7 in culture with LPS being stimulatory for this particular cytokine only during the first days of differentiation. Upon further cultivation of MAC up to 28 days, LPS-induced IL-1β levels remained very low, but IL-6 levels increased again reaching that of blood MO, and TNF-α continued to rise reaching levels up to 30-fold higher than in blood MO. M-CSF secretion stayed high with LPS even suppressing constitutive secretion. Long-term cultured MAC started to release IL-6 and TNF-α also in the absence of a stimulus and, furthermore, became responsive to IFN-g alone. Our data show that the release of each cytokine investigated is differently regulated during maturation. These results document the functional plasticity of human MAC and emphasize the impact that MO to MAC differentiation may have in vivo.