bluuebunny/crossref_metadata_2025_split huggingface dataset:
A neutrophil-derived proteolytic inactive elastase homologue (hHBP) mediates reversible contraction of fibroblasts and endothelial cell monolayers and stimulates monocyte survival and thrombospondin secretion
Authors: Østergaard Erik , Flodgaard Hans 
Published: January 2018

Abstract
Human heparin-binding protein (hHBP) is a recently discovered proteolytically inactive neutrophil elastase homologue with sequence identity to azurocidin and CAP37. The protein has antibacterial properties and chemotactic activity toward monocytes. In the present work, we show that monocytes, cultured under serum-free conditions, developed morphological changes and formed multicellular aggregates 4 h after the addition of hHBP at a concentration of 10 μg/ml. However, after prolonged incubation (11 days) with unchanged medium, the cells spread again. The hHBP-treated cells had a two- to threefold increase in survival compared to control cells, measured using trypan blue as an indicator of living cells. Differentiation of the alive cells to macrophages was detected by changes in morphology, a threefold increase in protein content, and a three- to fourfold increase in acid phosphatase activity. When monocytes in parallel experiments were labelled with [35S]methionine de novo synthesis and secretion of thrombospondin in a dose-dependent manner was observed after 16 h, with half-maximal secretion at 2 μg hHBP/ml and a maximal 12-fold increase in secretion with respect to controls at 16 μg/ml. Supplementary labeling with [35S]sulfate revealed that the same monocytes down-regulated the secretion of a large proteoglycan (300–400 kd), apparently also with a half-maximal decrease rate at 2 μg/ml hHBP. Exposure of confluent fibroblast and endothelial cell monolayers to hHPB (10 μg/ml) in the absence of fetal calf serum resulted in cell contraction leaving gaps between cells, the phenomenon being recognizable within 4 h after addition of hHBP. Addition of fetal calf serum to a concentration of 10% completely restored the monolayers. A unique role of hHBP in host defense involving recruitment of monocytes and a key funciton of hHBP in neutrophil extravasation in response to inflammatory chemotactic signals such as leukotriene B4, complement peptide G5a, and N-formyl-methionyl-leucyl-phenylalanine are suggested.
Pulmonary surfactant phospholipids modulate priming of rabbit alveolar macrophages for oxidative responses
Authors: Hayakawa Hiroshi , Giridhar Girish , Myrvik Quentin N , Kucera Louis 
Published: January 2018

Abstract
We investigated the effect of individual phospholipids contained in pulmonary surfactant (PS) on the macrophage-activating factor (MAF)-induced priming of rabbit alveolar macrophages (AMs) for oxidative responses elicited by phorbol myristate acetate (PMA) or opsonized zymosan (Op-Zym). AMs were incubated with MAF with or without phospholipids for 18 h. After incubation, oxidative responses were elicited with PMA (0.5 μg/ml) or Op-Zym (250 μg/ml) and monitored by chemiluminescence (GL) assays. The data indicate that natural surfactant inhibited MAF-induced priming of rabbit AMs for PMA- or Op-Zym-elicited oxidative responses. Artificial surfactant inhibited PMA-elicited CL responses but enhanced Op-Zym-elicited GL responses. Individual phospholipids differed in modulative activities. Dioleoyl phosphatidylcholine (DOPC), dipalmitoyl phosphatidylglycerol (DPPG), and phosphatidylinositol (PI) inhibited MAF-induced priming when the oxidative responses were elicited with PMA. Whereas DPPG inhibited Op-Zym-elicited oxidative responses, dipalmitoyl phosphatidylcholine (DPPC) and DOPC primed AMs for increased Op-Zym-elicited oxidative responses. DOPC did not affect the binding of phorbol dibutyrate to AMs, which suggests that reduced cell binding of phorbol ester was not responsible for the inhibition of PMA-elicited oxidative responses in AMs treated with DOPC. Similarly, DPPC, DOPC, and DPPG did not affect the number of zymosan particles phagocytosed by AMs compared to the control, which suggested that enhanced or reduced Op-Zym-elicited oxidative responses by phospholipids were not due to altered phagocytic activity of AMs. In conclusion, our data indicate that individual surfactant phospholipid differently modulates priming of AMs for oxidative responses, and the effect of individual phospholipids does not account for the effect of complete PS on priming of AMs.
Monocyte adherence to fibronectin: role of CD11/CD18 integrins and relationship to other monocyte functions
Authors: Owen Caroline A , Campbell Edward J , Stockley Robert A 
Published: January 2018

Abstract
Adherence of monocytes to extracellular matrix components is critical for their accumulation at sites of infection. To gain insight into the factors that regulate monocyte recruitment, we have studied monocyte adherence with regard to the regulatory effects of bacterial lipopolysaccharide (LPS) and the mechanisms involved; moreover, we have contrasted the phenotypes of adherent and nonadherent cells. Our results show that only a minor subpopulation of monocytes (20–25%) adhere spontaneously to fibronectin and that LPS stimulated a threefold increase in the proportion of adherent cells. Basal adherence and LPS-stimulated adherence of monocytes to fibronectin were substantially mediated by CD11/CD18 integrins. Further studies revealed that spontaneously adherent monocytes were 14-fold more actively phagocytic, released 1.6-fold more superoxide anion, and contained 20-fold more peroxidase activity than nonadherent cells, whereas LPS-adherent cells had an intermediate phenotype. These results indicate that LPS may enhance the accumulation of monocytes with an antimicrobial phenotype and thereby promote resolution of tissue infection.
Isolation of monocytic serine esterase and evaluation of its proteolytic activity
Authors: Salmassi Ali , Kreipe Hans , Radzun Heinz J , Lilischkis Richard , Charchinajad-Amoey Madjid , Zschunke Frank , Buck Friedrich , Lottspeich Friedrich , Parwaresch M Reza 
Published: January 2018

Abstract
Monocytes are characterized by high activity of α-naphthyl acetate esterase (ANAE), distinguishing them from all other blood cells. The physiological function of this monocyte marker enzyme has not yet been elucidated. In this study ANAE's potential proteolytic activity was anlayzed because serine esterases/proteases can function as effector molecules in cell-mediated cytotoxicity and because monocytes-macrophages are known to exert cytotoxic effects on tumor cells. This enzyme was purified from the monocytic cell line U-937 by preparative isoelectric focusing and a three-step high-performance liquid chromatography that conserved its catalytic activity. It has a molecular mass of 60 kd, and partial amino acid sequence revealed that the enzyme is not identical to known serine esterases/proteases. The purified enzyme failed to digest a couple of peptides, indicating lack of protease activity. In addition, the esterolytic activity of ANAE was not inhibited by protease inhibitors. The isolation and purification of ANAE enable further studies concerning its function in monocytes-macrophages and its relation to monocytic cytotoxicity.
Effector function of hepatocytes and Kupffer cells in the resolution of systemic bacterial infections
Authors: Gregory Stephen H , Barczynski Lisa K , Wing Edward J 
Published: January 2018

Abstract
It has been suggested that mononuclear phagocytes serve as the principal site of replication for a number of intracellular pathogens including Listeria monocytogenes. To determine the role of the tissue macrophages (Kupffer cells) in the proliferation of Listeria taken up in the liver, the hepatic cell populations were purified and the associated bacteria were quantified at periodic intervals postinfection. Here we report that the bulk of Listeria injected intravenously into nonimmune mice replicated within hepatocytes rather than Kupffer cells. Whereas a 200-fold increase in the number of hepatocyte-associated Listeria occurred during the first 3 days following infection, a relatively small (less than 2-fold) increase in number of Kupffer cell-associated Listeria was observed. The Listeria injected intravenously into immune animals, on the other hand, were eliminated rapidly from the hepatocyte as well as the Kupffer cell population. The latter findings suggest that uptake and elimination of pathogenic organisms by “nonprofessional phagocytes” in the liver (i.e., hepatocytes) may be an important effector mechanism in host defenses.
Cationic defensins arise from charge-neutralized propeptides: a mechanism for avoiding leukocyte autocytotoxicity?
Authors: Michaelson David , Rayner John , Couto Marcelo , Ganz Tomas 
Published: January 2018

Abstract
Defensins, small cationic polypeptides with antimicrobial and cytotoxic properties, are among the principal constituents of cytoplasmic granules of mammalian neutrophils and certain macrophages. To identify conserved structural features of defensin precursors that may be important for their targeting to cytoplasmic granules or for prevention of autocytotoxicity, we isolated and sequenced three neutrophil-specific rabbit defensin cDNAs that code for preproprotein precursors to the mature defensins NP-3a, NP-4, and NP-5. The preprodefensins NP-3a, NP-4, and NP-5, like the previously characterized preprodefensins, lack consensus sequences for N-linked glycosylation, suggesting that defensins are targeted to lysosome-like granules by a mechanism not dependent on the mannose-6-phosphate receptor. Analysis of all seven known myeloid prodefensins revealed a structure wherein an anionic propiece neutralizes the cationicity of the mature peptide. Because defensins apparently require cationic epitopes for cell membrane permeabilization and cytotoxicity, charge neutralization of mature peptides by their anionic propieces may prevent autocytotoxicity during defensin synthesis and processing.
Regulatory role of cytokines in IgE-mediated allergy
Authors: Tan Henkie P , Lebeck Lauralynn K , Nehlsen-Cannarella Sandra L 
Published: January 2018

Abstract
The discovery of immunoglobulin E (IgE) is considered the most important contribution, to date, in the field of clinical allergy. Studies in rodents and humans have suggested that IgE production could be regulated by antigen-specific helper and suppressor T cells and by isotype-specific factors having affinity for IgE. In recent years, the synthesis of IgE has been shown to be regulated, in part, by a cytokine network. This review summarizes the cytokines that up-regulate (interleukins-4, 5, and 6) and down-regulate (interferon-γ and interleukin-2) the production of IgE. Emphasis is placed on IL-4 and IFN-γ, two lymphokines known to play a major, but reciprocal, role in IgE synthesis. Increased insight into the various mechanisms of IgE control by cytokines and their receptors will eventually lead to improved treatment strategies in the clinical management of IgE-mediated allergy.
Tissue-specific expression of murine IP-10 mRNA following systemic treatment with interferon γ
Authors: Narumi Shosaku , Wyner Lawrence M , Stoler Mark H , Tannenbaum Charles S , Hamilton Thomas A 
Published: January 2018

Abstract
We have examined the tissue distribution of 10-kd inflammatory protein (IP-10) mRNA expression in C57Bl/6 mice injected intravenously (i.v.) with various inflammatory stimuli. IP-10 mRNA was strongly induced by interferon-γ (IFN-γ) in liver and kidney but only poorly in skin, heart, and lung. IFN-γ had nearly equivalent access to these tissues as indicated by the distribution of radiolabeled recombinant IFN-γ 1 h after injection. The time course of IP-10 mRNA appearance was rapid and transient in both liver and kidney; maximal expression in the liver (2 h) preceded that in the kidney (3 h) and declined rapidly thereafter in both tissues. Expression of IP-10 mRNA in the liver and kidney was highly sensitive to IFN-γ treatment; nearly maximal stimulation occurred with injection of 500 U of IFN-γ per mouse. Comparable stimulation of IP-10 mRNA expression in splenic macrophages required 10,000 U of IFN-γ administered i.v., indicating that liver and kidney responses are 10- to 20-fold more sensitive. IP-10 mRNA expression in both tissues was not restricted to stimulation by IFN-γ but was also seen with injection of lipopolysaccharide (LPS) (25 μg/mouse) or IFN-β (100,000 U/mouse). Two other members of the IP-10 gene family, KC (gro) and JE (MCP-1), were expressed at lower levels under similar treatment conditions. Analysis of IP-10 mRNA distribution in the liver and kidney by in situ hybridization indicated that expression in both tissues was most prominent in the reticuloendothelial cell system, particularly in the endothelial lining of the microvascular circulation. Although the function of the IP-10 gene product has not been defined, these results suggest that it may play an important role in the response of both the liver and kidney to systemic inflammation.
Impaired stimulus-response coupling in association with increased growth rate of HL60 cells
Authors: Hadjokas Nicholas , Bayer Clifford , Nielson Christopher P 
Published: January 2018

Abstract
Impairments in the respiratory burst and stimulus-response coupling were studied with respect to the increased rate of cell replication that occurred in HL60 cells during repetitive passages in cell culture. During a 45-week period of culture, HL60 cells developed a progressive increase in rate of replication. Concomitantly, undifferentiated cells developed an impairment in ATP-induced calcium mobilization. The percentage of cells that could be differentiated with dimethyl sulfoxide progressively diminished. Differentiated cells developed an impairment in both the respiratory burst and secretion of β-glucuronidase. In addition, regulation of the respiratory burst by cAMP agonists including isoproterenol, adenosine, and prostaglandin E2 was reduced in rapidly proliferating cells. Thus, multiple changes in stimulus-response coupling occur during cell culture in association with an increase in rate of cell replication. It may be important to recognize progressive impairments in cell function in studies using repetitive samples of HL60 cells from a continuously maintained cell population. The observed impairments in stimulus-response coupling may be relevant to unregulated cell growth in neoplastic disease.
Effect of lipopolysaccharide on transport and metabolism of arginine in mouse peritoneal macrophages
Authors: Sato Hideyo , Fujiwara Mari , Bannai Shiro 
Published: January 2018

Abstract
The transport activity of arginine in mouse peritoneal macrophages was strongly induced when they were cultured with 1 ng/ml bacterial lipopolysaccharide (LPS) for 12 h. Arginine in the medium decreased whereas ornithine in the medium increased during the culture. This time-dependent change of arginine to ornithine was accelerated by LPS. However, the activity of arginase in the macrophages did not change during the culture with or without LPS and release of arginase from the cells to the medium was not detected. It is suggested that the transport of arginine and ornithine was a rate-limiting step in arginine-to-ornithine conversion in the macrophage culture medium. A possible role of the induction of arginine transport activity in the macrophage cytocidal activity due to arginine depletion and nitric oxide production is discussed.
The myeloid leukemia cell line HL-60 produces a factor that induces chloride secretion in cultured epithelial cells
Authors: Colgan Sean P , Matthews Jeffrey B , Parkos Charles A , Delp Charlene , Awtrey Christopher S , Madara James L 
Published: January 2018

Abstract
When activated, polymorphonuclear leukocytes (PMNs) produce a small soluble factor, termed neutrophil-derived secretagogue (NDS), that elicits electrogenic Cl- secretion — the transport event responsible for hydration of mucosal surfaces. Work toward purification of this factor has been hampered by variability in activity of PMN-derived NDS. Using a human-derived intestinal epithelial cell line (T84) that serves as a model for studies of the regulation of electrogenic Cl- secretion, we find that the human promyelocytic leukemia cell line HL-60 secretes a factor with NDS-like activity. Buffer conditioned by HL-60 cells (107 cells/ml for 1 h), when applied to T84 monolayers grown on permeable supports and analyzed by routine electrophysiological techniques, elicited a short-circuit current (Isc) of 11.7 ± 1.02 μA/cm2. This short-circuit current was sensitive to bumetanide, an inhibitor of the basolateral Na-K-2CI cotransporter, and was dependent on the presence of chloride in the assay buffers. Such data indicate that buffer conditioned by HL-60 cells stimulates electrogenic Cl- secretion. Like NDS, the active factor in HL-60–conditioned buffer has a nominal molecular weight of less than 500 and was increased by activation of cells with phorbol ester. 125I and 86Rb efflux assays confirmed that the secretagogue released by stimulated HL-60 cells, similar to PMN-derived NDS, preferentially stimulates opening of Cl- rather than K+ channels in T84 cells. Lastly, release of NDS-like bioactivity increases when HL-60 cells are differentiated toward granulocytes compared to cells differentiated toward monocytes.
Lytic effects of Actinobacillus actinomycetemcomitans leukotoxin on human neutrophil cytoplasts
Authors: Iwase Masayasu , Korchak Helen M , Lally Edward T , Berthold Peter , Taichman Norton S 
Published: January 2018

Abstract
Actinobacillus actinomycetemcomitans leukotoxin lysed human neutrophil cytoplasts. The reaction was associated with a rapid influx of extracellular calcium, a collapse in membrane potential, release of lactate dehydrogenase, and overt disintegration of the plasma membrane. These functional and structural alterations in the plasmalemma of neutrophil cytoplasts reinforce the hypothesis that A. actinomycetemcomitans leukotoxin acts as a pore-forming, membranolytic agent and indicate that neutrophil cytoplasts are useful tools in studying the biology of membrane-active toxins.
Macrophage function in response to PGE2, L-arginine deprivation, and activation by colony-stimulating factors is dependent on hematopoietic stimulus
Authors: Rutherford Mark S , Schook Lawrence B 
Published: January 2018

Abstract
Different macrophage preparations were compared for functional capacity in conditions of high prostaglandin E2 (PGE2) or low l-arginine concentrations. Macrophages derived in vitro from bone marrow progenitor cells (bone marrow-derived macrophages, BMDMs) using colony-stimulating factor 1 (CSF-1) as the myelopoietic stimulus displayed a greater sensitivity to PGE2-induced suppression of tumor necrosis factor a (TNF-α) secretion than did macrophages derived using granulocyte-macrophage colony-stimulating factor (GM-GSF). Neither BMDM population was inhibited by PGE2 for the direct cytolysis of L929 cells (TNF-α sensitive), and only GM-CSF–derived macrophages showed decreased killing of TNF-α–resistant K562 targets. Exogenous cAMP inhibited TNF-α secretion, but not nitrite secretion, by both BMDM populations. GM-GSF–derived macrophages accumulated less cAMP following PGE2 treatment than did CSF-1–derived macrophages. Removing l-arginine from the medium did not inhibit cytotoxicity or PGE2 secretion, but the listeriacidal activity specific to interferon-γ plus lipopolysaccharide (LPS)-activated GM-CSF–derived macrophages was blocked by removal of l-arginine. Treatment with CSF-1 or GM-CSF alone did not activate the macrophages, but GM-CSF efficiently primed both BMDM populations for augmented TNF-α secretion in response to secondary stimulation using LPS. However, GM-CSF augmented the LPS-induced production of nitrite and PGE2 by CSF-1–derived macrophages only. These results demonstrate the potential for differential macrophage function within inflammatory sites based on the hematopoietic stimulus under which the macrophage is derived and the specific conditions present in the lesion.
Liposomes containing muramyl tripeptide phosphatidylethanolamine (MTP-PE) are excellent adjuvants for induction of an immune response to protein and tumor antigens
Authors: Ullrich Stephen E , Fidler Isaiah J 
Published: January 2018

Abstract
Liposomes containing the synthetic lipophilic analog of muramyl dipeptide, muramyl tripeptide phosphatidylethanolamine (MTP-PE), were used as adjuvants for the induction of humoral and cellular immune responses following immunization with protein or tumor antigens. Cellular immune reactions, including delayed- type hypersensitivity and lymphoproliferation in vitro, were observed following immunization of mice with a mixture of antigen and liposome-MTP-PE. Immunization with murine melanoma K1735 cells, admixed with liposomal MTP-PE, induced a protective immune response as demonstrated by the rejection of transplanted tumor cells. Antibody production was also induced following immunization with protein antigens admixed with liposome-MTP-PE. The efficacy of adjuvant activity following immunization with antigens admixed with liposome-MTP-PE was equal to or better than that of complete Freund's adjuvant (CFA). Moreover, liposome- MTP-PE did not have the toxic side effects associated with CFA. These data suggest that phospholipid liposomes containing MTP-PE are superior adjuvants and should receive consideration for vaccine therapy.
Activation of human monocyte chemiluminescence response by acylpoly(1,3)galactosides derived from Kiebsiella pneumoniae
Authors: Kouassi Edouard , Hmama Zakaria , Una Gérard , Vial Jean , Faure-Barba Florence , Normier Gérard , Binz Hans , Revillard Jean-Pierre 
Published: January 2018

Abstract
The stimulating activity of several preparations isolated from a membrane proteoglycan of a nonen- capsulated smooth strain of Klebsiella pneumoniae (Kp- MPG) on the oxidative burst of human blood monocytes was assessed by luminol-enhanced chemiluminescence (CL). Five Kp derivatives were studied: a 34-kd acyl- poly(l,3)galactoside (APG), obtained by drastic alkaline hydrolysis and purified by chromatography; an APG preparation subjected to acid hydrolysis that removed the core part and all fatty acids, leaving intact the galactose chain of APG (GC-APG); an APG preparation subjected to mild oxidation (ox APG); a preparation obtained by mild alkaline hydrolysis of Kp-MPG, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG); and a polymer of the latter compound, APG pol. EFA-APG directly stimulated monocyte CL, whereas Kp-MPG, APG pol, and the whole bacterial cells had little or no activity. APG itself and ox APG induced a weaker response than EFA-APG. Polymyxin B sulfate completely inhibited the CL response to bacterial lipopolysaccharide (LPS) but not to EFA-APG. The stimulating action of EFA-APG on blood monocytes was dependent on the extracellular levels of both calcium and magnesium. Preincubation of monocytes with monoclonal antibody anti-Mac-1 directed against CDllb, the αchain of complement receptor type 3 (CR3; CDllb/CD18), strongly inhibited CL activation by EFA-APG and to a lesser extent CL activation by un- opsonized zymosan and rough LPS. Altogether, these findings provide indirect evidence for the contribution of the CDllb/CD18 integrin in the functional interaction of EFA-APG with monocyte membranes. They demonstrate the role of fatty acids in the triggering of monocyte oxidative burst, while the polysaccharide chain itself does not contribute to induction of the CL response in this model. In keeping with the effects of EFA-APG and APG, we show that the monocyte CL response was triggered by bacterial LPS from the rough strain of Salmonella minnesota Re 595 and its lipid A, but not by LPS from smooth strains, again suggesting a critical role for the lipid moiety.