bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two Distinct Cytolytic Mechanisms of Macrophages and Monocytes Activated by Phorbol Myristate Acetate
Authors: Chung Tejune , Kim Yoon B 
Published: January 2018

Abstract
Pulmonary alveolar macrophages (PAM) and peripheral blood monocytes (PBMO) of the miniature swine can be converted to cytolytically active effector cells by treating with phorbol myristate acetate (PMA) as determined by enhancement of cytotoxicity to various target cells. Kinetics of the PMA-activated PAM and PBMO in cytotoxicity show that the effective PMA concentration ranges from 10 to 1,000 ng/ml. Induction of cytotoxic macrophages and monocytes occurred as early as 30 min and to their maximum cytotoxicity after 1 hr exposure to PMA and the enhanced cytotoxic activity persisted up to 24 to 40 hr when PMA was removed by washing after 1 hr exposure, but prolonged exposure to PMA for more than 6 hr resulted in a drastic decrease of cytolytic activities suggesting the prolonged exposure to PMA causes macrophages and monocytes to become refractory to PMA stimulation. Target cells displayed varying degrees of cytotoxic sensitivity to the PMA-activated PAM and PBMO; PRBC, SRBC, and K562 were sensitive, WEHI-164 and U937 were relatively sensitive, and SB was very resistant to these activated effector cells. The mechanisms of PMA-induced cytotoxicity could largely be divided into two categories. One was the H2O2 mediated killing as shown by complete reduction of cytotoxicity after adding catatase in the assay. The other was the proteases mediated cytolysis, which could be blocked by protease inhibitors, Phenyl methyl sulfonyl fluoride (PMSF), and N- α-p-tosyl-L-lysine chloromethyl ketone (TLCK). H2O2 was the only mediator produced in large enough quantities from PBMO to kill target cells, whereas PAM could produce both mediators (H2O2 and proteases). PRBC, SRBC, and K562 appeared to be killed by H2O2 produced by PAM and PBMO. In contrast, U937 and WEHI-164 appeared to be killed by proteases in PAM mediated cytolysis but by H2O2 in PBMO-mediated cytolysis. These results suggest that the observed cytolytic mechanisms can be differed by type of target cells as well as the source of mononuclear phagocytes within the individual animal.
Influence of Platelet Activating Factor and a Nonmetabolizable Analogue on Superoxide Production by Bone Marrow Derived Macrophages
Authors: Storch J , Ferber E , Munder P G 
Published: January 2018

Abstract
Serum-free cultured macrophages could be stimulated for lucigenin-dependent chemiluminescence by platelet activating factor (PAF) and phorbol myristate acetate (PMA). Stimulation with PMA resulted in a desensitization against PAF, whereas prestimulation with PAF had no influence on a following response caused by PMA. The PAF analogue, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (Et-18-OCH3), did not induce chemiluminescence by itself and desensitized the cells against PAF, like substimulating concentrations of PAF. PAF and PMA responsiveness was rapidly modulated in a similar manner during adherence of the cells to polystyrene tubes. At higher concentrations, Et-18-OCH3 as well as lysophosphatidylcholines potentiated PMA-induced chemiluminescence. The PAF analogue was most effective. Although PMA-induced chemiluminescence was stimulated at least 5-fold by Et-18-OCH3, this compound Increased the PMA-induced activation of protein kinase C only 1.39-fold. The priming effect of Et-18-OCH3 was not reduced in the absence of extracellular Ca2+ and after cell membrane depolarisation.
Infection of a Murine T-Cell Line With a Retrovirus Carrying c-myc Decreases the Interleukin-2 Cell Dependence by a Nonautocrine Mechanism
Authors: Shapiro Ilya M , Winberg Gösta , Stefanescu Irina , Wigzell Hans , Menezes José 
Published: January 2018

Abstract
A murine Interleukin-2 (IL-2)-dependent T-cell line, CTLL-2, was infected with a retrovirus carrying the mouse c-myc cDNA and the Tn-5 neogene. Transduced cells were selected in the presence of Geneticin sulfate (G418); these cells were shown to express both the endogenous and the transduced c-myc genes. The IL-2 requirement of these cells was then found to be significantly reduced. The cells did not express IL-2 mRNA nor did they produce an activity myogenic for CTLL-2 cells. This suggests that the reduction of IL-2 dependence observed following retroviral transduction of c-myc is caused by a nonautocrine mechanism.
Virus-Induced Enhancement of Arachidonate Metabolism by Bovine Alveolar Macrophages In Vitro
Authors: Laegreid W W , Taylor S M , Leid R W , Silflow R M , Evermann J R , Breeze R G , Liggitt H D 
Published: January 2018

Abstract
Virus infection of alveolar macrophages both in vivo and in vitro has been associated with a variety of changes in cellular function. Some of these changes are identical to the effects that arachidonate-derived mediators, prostaglandins, leukotrienes, and hydroxyeicosatetraenoic acids, have on macrophage function. Virus infection of macrophages has been previously shown to increase the output of some arachidonate metabolites, most notably PGE2. However, the effect of virus infection on arachidonate metabolism in general has not been well described. In our experiments, primary cultures of alveolar macrophages obtained from normal cattle by bronchoalveolar lavage, were infected in vitro with parainfluenza type 3 virus. At days 0 to 4 post-infection (p.i.) these cells were labelled with 3H-arachidonic acid and stimulated with either serum-coated zymosan, the calcium ionophore A23187, or phorbol myristate acetate. The complete spectrum of arachidonate-derived metabolites was determined by reverse-phase high performance liquid chromatography with UV and on-line radiometric monitoring of column eluant. The total output of metabolites of arachidonic acid by virus-infected alveolar macrophages was increased over that of noninfected controls (with all stimuli tested) by day 4 p.i. (P ≤ 0.05). The production of metabolites by the cyclooxygenase, 12-and 5-lipoxygenase enzyme systems was significantly increased, as was the release of 3H-arachidonate. The lack of stimulus specificity and the increases in arachidonate release suggest that greater substrate availability, due either to increased phosphollpase activity or direct virus-membrane interaction, may be responsible for the virus-induced enhancement of metabolite output.
Leukocyte Function in Pelger-Huët Anomaly of Dogs
Authors: Latimer Kenneth S , Kircher Ingrid M , Lindl Patricia A , Dawe Donald L , Brown John 
Published: January 2018

Abstract
Leukocyte function was evaluated in five dogs with Pelger-Huët (P-H) anomaly and in five control dogs. No significant differences were found between groups in neutrophil adherence, random movement, chemotaxis, phagocytosis, or bacterial killing of Staphylococcus intermedius. Neutrophils migrated rapidly into inflammatory sites where progressive nuclear lobulation was noted over time. Antibody titers to exogenous antigens were similar in the P-H and control groups indicating B- and T-lymphocyte cooperation in humoral immunity. Lymphocyte blastogenesis to phytohemagglutinin also was similar in both groups suggesting the presence of a responsive T-lymphocyte population. These findings indicate that no apparent predisposition to infection or immunodeficiency exists in dogs with P-H anomaly.
1,25-Dihydroxyvitamin D3 Induces Responsiveness to the Chemotactic Peptide f-Met-Leu-Phe in the Human Monocytic Line U937: Dissociation Between Calcium and Oxidative Metabolic Responses
Authors: Polla Barbara S , Werlen Guy , Clerget Michel , Pittet Didier , Rossier Michel F , Capponi Alessandro M 
Published: January 2018

Abstract
In the human premonocytic line U937, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) induces a functional NADPH oxidase, that is responsive to both phorbol esters and opsonized zymosan. The chemotactic peptide f-Met-Leu-Phe (fMLP) did not. however, induce superoxide generation by these cells. This was not due to the absence of receptors for fMLP. Although there was no significant binding of [3H]-fMLP to undifferentiated U937 cells, preincubation with 1,25-(OH)2D3 induced expression of specific and saturable binding sites. Moreover, fMLP induced a rapid and reversible rise in cytosolic free Ca1+ concentration ([Ca2+]i) in 1,25-(OH)2D3-treated U937 cells, but not in control or 24,25-dihydroxyvitamin D3 (24,25-(OH)sD3)-treated cells. This [Ca2+]i response was dependent on concentrations of both fMLP and 1,25-(OH)2D3 and was observed at physiologic concentrations of the hormone (25 pM). The rise in [Ca2+]i induced by fMLP in 1,25-(OH)2D3-treated U937 cells was blocked by pertussis toxin and presumably mediated by inositol (1,4.5)-trisphosphate generation. These results indicate that in U937 cells differentiated with 1,25-(OH)2D3, inositol phosphate-mediated [Ca2+]i responses to fMLP are uncoupled from NADPH oxidase activation.
Both Recombinant Interleukin-1 (Beta) and Purified Human Monocyte Interleukin-1 Prime Human Neutrophils for Increased Oxidative Activity and Promote Neutrophil Spreading
Authors: Sullivan Gail W , Carper Holliday T , Sullivan James A , Murata Teizo , Mandell Gerald L 
Published: January 2018

Abstract
Both purified human monocyte interleukin-1 and recombinant interleukin-1 (beta) primed neutrophils for increased superoxide production and chemiluminescence in response to f-met-leu-phe. In addition, purified human monocyte interleukin-1 and recombinant interleukin-1 (beta) altered neutrophil shape. Recombinant interleukin-1 (alpha) used at the same concentration of interleukin-1 (beta) did not prime neutrophils for increased superoxide production after stimulation with f-met-leu-phe. interleukin-1 expressed by monocytes in response to endotoxin stimulation could act as a modulator of neutrophil function.
Macrophage Function in Murine Allogeneic Bone Marrow Radiation Chimeras in the Early Phase After Transplantation
Authors: Roesler Joachim , Baccarini Manuela , Vogt Birgit , Lohmann-Matthes Marie-Luise 
Published: January 2018

Abstract
We tested several of the functions of macrophages (Mφ) in the early phase after allogeneic bone marrow transfer to get information about this important aspect of the nonspecific immune system in the T-cell-deficient recipient. On days 3-5 after transfer, the number of Mφ was reduced in the spleen, liver, lungs, and peritoneal cavity (Pe). The phagocytosis of sheep red blood cells (SRBC) by these Mφ was normal or even enhanced, as in the case of Pe-Mφ. Already on days 8-12 after transfer, the number of Mφ in spleen and liver exceeded that of controls, whereas the number was still reduced in lungs and Pe. We examined their ability to kill P815 tumor cells, to produce tumor necrosis factor-α (TNFα), to phagocytose SRBC, to produce reactive oxygen intermediates (ROI) in vitro and to kill Listeria monocytogenes in vivo. Most functions were normal and often even enhanced, depending on the organ origin, but the ability of Pe-Mφ to produce ROI was reduced. Proliferative response to macrophage colony-stimulating factor (M-CSF) and killing of YAC-1 tumor cells revealed a high frequency of macrophage precursor cells in the spleen and liver and a high natural killer (NK) activity in the liver. Altogether, enhanced nonspecific immune function, especially preactivated Mφ, may enable chimeras to survive attacks by opportunistic pathogens.
Pertussis Toxin Inhibits the FMLP-lnduced Membrane Association of Protein Kinase C in Human Neutrophils
Authors: Christiansen Niels Obel 
Published: January 2018

Abstract
The effect of pertussis toxin on N-formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol 12-myristate 13-acetate (PMA), ionomycin, and A23187-induced translocation of protein kinase C and superoxide generation was studied in human neutrophils. Pertussis toxin was shown to inhibit FMLP-induced superoxide generation in parallel with an inhibition of protein kinase C translocation. In contrast, no effect of pertussis toxin was demonstrated upon superoxide generation or protein kinase C translocation in PMA-, A23187-, or ionomycin-stimulated cells. In that superoxide generation and protein kinase C translocation were inhibited in parallel, it is concluded that a G-protein-dependent cascade is involved in the FMLP-induced activation of protein kinase C, and this cascade may be equivalent to the pathway inducing superoxide generation.
Thymic Stroma-Derived T Cell Growth Factor (TSTGF): III. Its Ability to Promote T Cell Proliferation Without Stimulating Interleukin 2- or 4-Dependent Autocrine Mechanism
Authors: Kosaka Hiroshi , Ogata Masato , Sano Haruo , Sakuma Shozo , Mizushima Yumiko , Nakamura Etsuo , Teraoka Hiroshi , Hamaoka Toshiyuki , Fujiwara Hiromi 
Published: January 2018

Abstract
A thymic stroma-derived cell clone, MRL104.8a produced a T cell growth factor designated as thymic stroma-derived T cell growth factor (TSTGF). This factor that is distinct from previously described T cell growth factors such as interleukin (IL) 2 or 4 was capable of promoting the growth of IL2-dependent, antigen-specific helper T cell clones. While such growth promotion was induced without requirement of the relevant antigen and exogenous IL2, we further investigated whether it depended on activation of an IL2- or IL4-dependent autocrine mechanism. Helper T cell clones, 8-E and 8-5, were able to proliferate in response to stimulation with either antigen or TSTGF. 8-E and 8-5 produced IL2 and IL4, respectively, in cultures following antigenic stimulation, whereas neither IL2 nor IL4 activity was detected in cultures during TSTGF-induced proliferation. The proliferation of these helper T cell clones by antigenic stimulation was almost completely inhibited when anti-IL2 receptor or anti-IL4 antibody was added to the cultures. The addition of cyclosporin A (CsA) to cultures of 8-E and 8-5 clones together with antigen also resulted in the complete inhibition of cellular proliferation in association with the suppression of IL2 and IL4 production. In contrast, TSTGF-induced proliferation was not affected by addition of either type of antibody or CsA. These results indicate that TSTGF is a novel T cell growth factor that can exert its own growth-promoting effect without depending on an IL2- or IL4-operating autocrine mechanism.
Heterogeneity in Responses of Human Blood Monocytes to Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Inamura Noriaki , Sone Saburo , Okubo Akio , Singh Sukh Mahendra , Ogura Takeshi 
Published: January 2018

Abstract
Granulocyte-macrophage colony-stimulating factor (GM-CSF) has stimulatory effects on various monocyte functions. We examined whether all or only some blood monocytes could respond to GM-CSF. Monocytes from peripheral blood of healthy donors were separated by size into five fractions by counter-flow centrifugal elutriation (CCE). The phagocytic activities of monocytes in these fractions depended on the size of the cells. On activation by bacteria-derived stimuli, these fractions showed similar responses of production of monokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) and cytotoxicity against allogeneic tumor cells. On treatment of these fractions with optimal concentration of GM-CSF, fractions 3, 4, and 5 showed tumoricidal activity and produced cell-associated IL-1, fraction 3 producing the most, whereas release of IL-1 and TNF in the supernatant was not observed. The cell-associated IL-1 was identified as IL-1α, not IL-1β, by neutralizing tests with antisera against IL-1α and IL-1β. GM-CSF also induced the proliferative and colony-forming responses of medium and large monocytes. These observations suggest that adoptive therapy with macrophage progenitor cells in peripheral blood may be useful in combination with GM-CSF for treatment of monocytopenia after chemotherapy or radiation therapy.
Ultrastructural and Immunocytochemical Study of the Uptake and Distribution of Bacterial Lipopolysaccharide in Human Monocytes
Authors: Kang Yuan-Hsu , Dwivedi R S , Lee Che-Hung 
Published: January 2018

Abstract
Interaction of bacterial lipopolysaccharide (LPS) with monocytes stimulates production of a variety of mediators that are involved in the pathogenesis of septic shock and wound repair. We report here the mechanisms of LPS uptake and intracellular distribution of LPS in human monocytes. Ficoll-Hypaque-purified peripheral mononuclear cells (PBMC) were exposed to LPS from rough Escherichia coli (J5) or to biotin-conjugated LPS (biotin-LPS) from smooth E. coli (0111:B4), or to fluorescein isothiocyanate-conjugated LPS of E. coli (055:B5) at 37° for various times and processed for electron microscopy, immunocytochemistry, and flow cytometry. Monocytes were identified by the presence of numerous cytoplasmic peroxidase-positive granules or by monoclonal antibodies against monocyte. LPS micelles were identified by their specific bilayer structure, staining of horseradish peroxidase reaction product, or colloidal gold using biotin-LPS or a monoclonal antibody to LPS. Binding of LPS to cell surface was observed 5 min after incubation with LPS. Intracellular localization of LPS micelles was found 30 min following exposure to LPS. Prolonged incubation with LPS increased intracellular LPS. Intracellulary, LPS micelles were found in large membrane-bound vacuoles, in small vesicles, and in the cytoplasm and nucleus. They were also observed in association with the cytomembrane of various organelles. The overall results indicate that LPS may be taken up by monocytes by direct passive diffusion through ruptures of plasma membrane, pinocytosis, and phagocytosis, involving specific and/or nonspecific binding, and suggest that peripheral blood monocytes play an important role in clearance of LPS; that LPS may have broad effects on cell functions; and that the nonspecific binding to various cytomembranes may be destructive to cell organelles and cells in general.
Effects of Inflammatory Cytokines and Phorbol Esters on the Adhesion of U937 Cells, a Human Monocyte-Like Cell Line, to Endothelial Cell Monolayers and Extracellular Matrix Proteins
Authors: Cavender Druie E , Edelbaum Dale , Welkovich Linda 
Published: January 2018

Abstract
The accumulation of mononuclear phagocytes at sites of chronic inflammation is dependent on an increase in the rate of extravasation of blood-borne monocytes through the vascular endothelium into the connective tissue. Once the monocytes have emigrated into the connective tissue, they may differentiate into tissue macrophages, presumably following interactions with extracellular matrix proteins. To study these processes, we tested the effects of cytokines and phorbol esters on the adhesion of U937 cells, a human monocyte-like cell line, to cultured endothelial cells (EC) and to matrix proteins. In the absence of cytokines, very few of the U937 cells adhered to EC (5% or less in most experiments). When EC were pretreated for optimal periods of time (4–8 hr) with recombinant interleukin-1α (IL-1α), IL-1β, tumor necrosis factor-α (TNFα), or lymphotoxin (LT; also known as TNF-β), 35–85% of the U937 cells were able to bind. Interferon-γ (IFN-γ) and interleukin–2 (IL-2) did not stimulate U937-EC binding, even though IFN-γ was shown to increase EC adhesiveness for T lymphocytes. Phorbol esters also greatly stimulated U937-EC adhesion but, in this case, the increase was due to an action on the U937 cells. A monoclonal antibody (MAb), 60.3, against the CD11/CD18 family of leukocyte adhesion molecules partially inhibited the adhesion of untreated and phorbol ester-treated U937 cells to noncytokine-treated EC. However, that MAb had no effect on U937 cell binding to TNF-α-treated EC. Thus U937 cells use both CD11/CD18-dependent and -independent mechanisms to adhere to EC. In the absence of stimulating agents, only a small proportion of the U937 cells (2–20%) adhered to fibronectin (FN), and almost none bound to either laminin (LN) or gelatin (denatured type I collagen). In the presence of phorbol esters, a much larger proportion of the U937 cells adhered to FN, with only slight increases in the proportion of cells which bound to LN or gelatin. Additional adhesion assays performed in the presence of a pentapeptide containing the amino acid sequence arg-gly-asp (RGD), which is part of one of the cell-binding domains of FN, demonstrated that the RGD-containing peptide almost totally blocked the phorbol ester-induced adhesion of U937 cells to FN. In contrast, the peptide had no inhibitory effect on the phorbol ester-induced binding of U937 cells to EC.
Entry of Human Immunodeficiency Virus-1 Into Glial Cells Proceeds via an Alternate, Efficient Pathway
Authors: Harouse Janet M , Laughlin Mark A , Pletcher Charles , Friedman Harvey M , Gonzalez-Scarano Francisco 
Published: January 2018

Abstract
Although the CD4 molecule is the cellular receptor for human immunodeficiency virus-1 (HIV-1) in cells of the lymphocyte/monocyte lineage, a number of investigators have also been able to infect cells, including several of central nervous system (CNS) origin, that do not express CD4 protein or mRNA. These infections are generally nonpermissive. To ascertain whether the nonpermissive nature of infection in glial cells is due to an inefficient entry pathway, we prepared a permanently transfected U373-MG cell line expressing the CD4 molecule and demonstrated that HIV-1 still replicates at a low level. Furthermore, a virus uptake assay indicated that HIV-1 enters glial cells effectively, even in the absence of CD4. These results demonstrate that HIV-1 entry is efficient and that the restrictive nature of the infection in glial cells is due to postentry mechanisms. In addition, these findings support the existence of an alternate, efficient, entry pathway in some glial cells.
L-Arginine-Dependent Production of a Reactive Nitrogen Intermediate by Macrophages of a Uricotelic Species
Authors: Sung Yen-Jen , Hotchkiss Joseph H , Austic Richard E , Dietert Rodney R 
Published: January 2018

Abstract
L-arginine-dependent production of reactive nitrogen intermediates (RNIs: nitric oxide, nitrite, and nitrate) by mammalian macrophages has been proposed to occur via an L-arginine oxidative deimination pathway and is known to be responsible for certain antineoplastic and antimicrobial effector functions. The present study represents the first examination of this pathway in a non-mammalian vertebrate. Because chickens, unlike mammals, lack a urea cycle and are incapable of de novo synthesis of L-arginine, the possible existence of an avian macrophage pathway for production of RNIs is questionable. We have defined conditions under which chicken macrophages are able to produce nitrite. Sephadex-elicited chicken peritoneal macrophages required a bacterial Ii-popolysaccharide (LPS from Escherichia coli) signal to produce nitrite during 24 hour cultures in the presence of L-arginine. As little as 5 ng/ml LPS resulted in significant nitrite production in culture. The relationship of nitrite production to both LPS and L-arginine levels was dose-dependent. D-arginine was unable to substitute for L-arginine but also produced no inhibitory effect In contrast, L-NG-monomethyl arginine showed a significant inhibitory effect on nitrite production. A virus-transformed chicken macrophage cell line, HD11, also produced nitrite in a dose-dependent manner relative to both LPS and L-arginine concentration. Concentrations as low as 5 ng/ml LPS and 0.1 mM L-arginine resulted in significant nitrite production, while maximum levels of nitrite production were obtained using ≥0.5 μg/ml LPS and ≥0.4 mM L-arginine. These results indicate that chicken macrophages can produce RNIs. This production is dependent upon activation and is influenced by local L-arginine concentration. Moreover, because the chicken does not possess the ability to synthesize arginine and has an absolute nutritional requirement for this amino acid, the chicken represents a highly controllable system to examine the in vivo effects of L-arginine on macrophage-related immune functions.