bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoids Fail to Inhibit Arachidonic Acid Metabolism Stimulated by Hydrogen Peroxide in the Alveolar Macrophage
Authors: Sporn Peter H S , Murphy Teresa M , Peters-Golden Marc 
Published: January 2018

Abstract
We have previously demonstrated that the biologically important oxidant hydrogen peroxide (H2O2) triggers release and metabolism of arachidonic acid (AA) in the alveolar macrophage (AM). In this study, we evaluated the ability of glucocorticoids to inhibit rat AM AA metabolism stimulated by H2O2, as compared to the particulate zymosan. Methylprednisolone and other glucocorticoids failed to significantly inhibit release of AA stimulated by H2O2. while markedly reducing AA release in response to zymosan. Similarly, methylprednisolone only weakly inhibited synthesis of thromboxane (Tx)B2 stimulated by H2O2, while inhibiting zymosan-induced eicosanoid synthesis to a marked degree. On the other hand, the phospholipase inhibitor mepacrine strongly inhibited AA release and TxB2 formation stimulated by both H2O2 and zymosan, indicating that H2O2-induced AA metabolism is indeed susceptible to pharmacologic inhibition. The failure of glucocorticoids to inhibit AA metabolism stimulated by H2O2 in the AM may in part explain their inability to ameliorate oxidant-mediated lung inflammation and injury.
Constitutive Expression of Interleukin-7 mRNA and Production of IL-7 by a Cloned Murine Thymic Stromal Cell Line
Authors: Sakata Tsuneaki , Iwagami Shoji , Tsuruta Yuji , Teraoka Hiroshi , Tatsumi Yoichi , Kita Yasumichi , Nishikawa Shin-Ichi , Takai Yasuyuki , Fujiwara Hiromi 
Published: January 2018

Abstract
Mouse interleukin-7 (IL-7) cDNA was cloned from mouse thymic stromal cell clone MRL104.8a using a polymerase chain reaction (PCR) technique and expressed in COS-7 cells. The resulting recombinant interleukin-7 (rlL-7) supported the proliferation of mouse antigen-specific helper T cell (Th) clone 9–16 in the absence of IL-2 and antigen as well as mouse pre-B cell line DW34. It was also found that high levels of the mRNA for IL-7 were constitutively expressed in the MRL104.8a cells, and a potent amount of IL-7 was produced in its culture supernatant. These results provide the evidence for constitutive expression of IL-7 mRNA and for production of IL-7 by thymic stromal cells that have a critical role in intrathymic T cell development. The results are discussed in the context of the functional and molecular relationship between IL-7 and the previously described cytokines produced by thymic stromal cells.
Effects of Adenosine on Inositol 1,4,5-Trisphosphate Formation and Intracellular Calcium Changes in Formyl-Met-Leu-Phe-Stimulated Human Neutrophils
Authors: Walker Blair A M , Hagenlocker Brian E , Douglas Vonda K , Ward Peter A 
Published: January 2018

Abstract
In the presence of adenosine, formyl-Met-Leu-Phe-stimulated human neutrophils show a greatly diminished production of superoxide anion. Analysis of changes in levels of intracellular calcium revealed that the immediate increase (occurring within seconds) in intracellular calcium following addition of formyl-Met-Leu-Phe is not affected by the presence of adenosine, although there are significantly lower intracellular calcium levels during the late phase (occurring 1–4 min after addition of formyl-Met-Leu-Phe). Consistent with these findings is the fact that adenosine does not affect the production of inositol 1,4,5-trisphosphate in formyl-Met-Leu-Phe-stimulated neutrophils. These data suggest that the profound inhibitory effects of adenosine on superoxide responses in formyl-Met-Leu-Phe-stimulated neutrophils may be related to an action of adenosine occurring late in the sequence of events of signal transduction.
Influence of Extracellular Calcium on the Metabolism of Arachidonic Acid in Alveolar Macrophages
Authors: Taylor Stephen M , Laegreid William W , Englen Mark D , Dani Ginger M , Silflow Ron M , Liggitt H Denny , Leid R Wes 
Published: January 2018

Abstract
Bovine alveolar macrophage metabolism of arachidonic acid (AA) via cyclooxygenase (CO) and lipoxygenase (LO) pathways is stimulus specific. Under standard conditions with RPMI-1640 media containing 0.4 mM Ca2+, the calcium ionophore A23187 stimulates the release of both CO and LO products, whereas opsonized zymosan and phorbol myristate acetate (PMA) selectively stimulate the CO pathway in these cells. We have examined the effect of varying the extracellular concentration of calcium (0–2.4 mM) on the profiles of AA metabolites secreted with differing stimuli. All stimuli caused the release of CO products, even in the absence of calcium in the media. The magnitude of release was correlated with increasing extracellular calcium concentrations, indicating some dependence of phospholipase activation on extracellular calcium. However, there were notable differences between stimuli regarding the magnitude of CO product formation and dependence on extracellular Ca2+. No 5-LO products were demonstrable with either zymosan or PMA at any concentration of extracellular calcium tested, and inhibition of CO by indomethacin did not result in 5-LO product formation for these stimuli. The production of 5-LO products in bovine alveolar macrophages by A23187 required extracellular calcium, demonstrating an absolute dependence for activation of the 5-LO pathway on an influx of extracellular calcium. Our results indicate that intracellular and extracellular Ca2+ have differing roles in the metabolism of AA down CO and LO pathways in bovine alveolar macrophages depending on the stimulus used. This regulation suggests that the pools of calcium required for activation of phospholipase A2 (PLA2) are not necessarily available for the 5-LO enzyme.
Stimulation of a Histone H4 Protein Kinase in Triton X-100 Lysates of Rabbit Peritoneal Neutrophils Pretreated With Chemotactic Factors: Effect of Leukotriene B4 and Cytochalasin B
Authors: Huang Chi-Kuang , Laramee Gary R 
Published: January 2018

Abstract
The effects of leukotriene B4 on the stimulation of a histone H4 kinase activity in rabbit peritoneal neutrophils have been studied. LTB4 activated the kinase within 10 sec with the increasing activity decaying to near basal level after 20 sec of stimulation. The effect was not inhibited by removal of extracellular calcium or loading the cells with quin-2/AM. Pretreatment of the cells with cytochalasin B greatly enhanced and prolonged the activation of the kinase. Pretreatment of the cells with LTB4 or fMet-Leu-Phe inhibited the effect of the later addition of LTB4. Since similar characteristics of LTB4 and cytochalasin B have also been observed in LTB4-stimulated responses such as secretion and superoxide generation, the results suggest a potential role of H4 kinase in LTB4-stimulated responses.
Immune Regulation by Platelet-Activating Factor: II. Mediation of Suppression by Cytokine-Stimulated Endothelial Cells In Vitro
Authors: Lacasse Chantal , Rola-Pleszczynski Marek 
Published: January 2018

Abstract
Human umbilical vein endothelial cells (EC) can respond to endotoxin or to the inflammatory cytokines tumor necrosis factor (TNF) and interleukin 1 (IL-1) by producing platelet-activating factor (PAF). When EC were preexposed to TNF-α (25 U/ml) for 1 h, and then washed, their subsequent coculture with peripheral blood mononuclear cells (PBMC) resulted in suppressed proliferative response of the latter to the mitogen Con A (P &lt; 0.05). This effect was completely reversed by the concomitant use of the PAF receptor antagonist BN 52021 (0.1 mM). Preexposure of EC to IL-1β (0.5 U/ml) induced similar effects, but IL-1 and TNF were not additive. Removal of monocytes from the PBMC population abolished the effects. On the other hand, coculture of monocytes with cytokine-preexposed EC resulted in significant induction of suppressor activity on lymphocyte proliferation. Our data indicate that EC, preexposed to inflammatory cytokines, can modulate lymphocyte functions via the production of PAF and its action on monocytes.
Chemotactic Activity and Receptor Binding of Neutrophil Attractant/Activation Protein-1 (NAP-1) and Structurally Related Host Defense Cytokines: Interaction of NAP-2 With the NAP-1 Receptor
Authors: Leonard Edward J , Yoshimura Teizo , Rot Antal , Noer Kathleen , Walz Alfred , Baggiolini Marco , Walz Daniel A , Goetzl Edward J , Castor C William 
Published: January 2018

Abstract
Neutrophil attractant/activation protein-1 (NAP-1) has sequence similarity to platelet factor-4 (PF-4) and to NAP-2 (a truncated form of connective tissue activating protein-Ill [CTAP-III(des 1–15)]. We compared chemotactic activity for neutrophils of these related proteins. We also included for comparison CTAP-III, CTAP-III(des 1–13), the C-terminal dodecapeptide of PF-4 [PF-4(59–70)], and C5a. Chemotactic potency (EC50) was highest for NAP-1 and C5a. Although chemotactic efficacy (peak percentage of neutrophils migrating) was comparable for C5a, NAP-1, and NAP-2, the NAP-2 response occurred only at concentrations 100-fold higher than the NAP-1 EC50 of 10-8 M. Data for the CTAP-III proteins confirmed that CTAP-III is not an attractant and that chemotactic activity appears as a result of cleavage of residues at the N-terminus to make CTAP-III(des 1–13) or NAP-2 [CTAP-III(des 1–15)]. Chemotactic activity of PF-4 was low and variable, with no significant response by neutrophils from six of nine subjects. In contrast, PF-4(59–70) regularly induced high chemotactic responses, although the EC50 of 1.6 × 10-5 M was 1,000-fold greater than that of NAP-1. The binding of fluoresceinated NAP-1 to neutrophils was inhibited by unlabeled NAP-1 or NAP-2 but not by PF-4 or PF-4 (59–70). This suggests that NAP-2 interacts with the neutrophil NAP-1 receptor. Despite the low chemotactic potency of NAP-2, it is a potential attractant at sites of injury because of the relatively large amounts of the parent CTAP-III released from platelets, as indicated by a serum concentration of approximately 10-6 M.
In Vitro Modulating Effect of Human Very-Low-Density Lipoproteins on Human Polymorphonuclear Leukocyte Oxidative Metabolism and Migration
Authors: Idohou N , Couderc R , Roch-Arveiller M , Bonneau C , Giroud J P , Raichvarg D 
Published: January 2018

Abstract
In this work, the in vitro effects of very-low-density lipoproteins (VLDL) on human polymorphonuclear leukocyte (PMN) oxidative metabolism and migration were studied.
VLDL stimulated PMN superoxide generation in absence of other stimulating agents. The effect of VLDL from normotriglyceridemic subjects was more marked than with VLDL from hypertriglyceridemia subjects.
VLDL reduced in a dose-dependent manner the luminol-dependent chemiluminescence of PMN stimulated by phorbol myristate acetate (PMA) and, to a lesser degree, by opsonized zymosan. This effect was observed with VLDL concentrations found in healthy and hypertriglyceridemic patients. Superoxide anion generation was also reduced by preincubation of PMN with VLDL before stimulation with PMA but not opsonized zymosan. VLDL were not cytotoxic for PMN. The above effects appear to be an intrinsic property of VLDL and might lead to reduced PMN-mediated non-specific host defences in hypertriglyceridemic subjects.
Proteolysis of Gelatin-Bound Fibronectin by Activated Leukocytes: A Role for Leukocyte Elastase
Authors: Daudi Imbesat , Gudewicz Paul W , Saba Thomas M , Cho Eshin , Vincent Peter 
Published: January 2018

Abstract
Fragmentation of subendothelial matrix-bound fibronectin by proteases released from stimulated leukocytes has been implicated in lung vascular injury. We studied the degradation of fibronectin bound to denatured collagen by inflammatory polymorphonuclear leukocytes (PMNL). Tissue culture wells coated with denatured collagen (gelatin) were pretreated with 125I rat plasma fibronectin to allow for fibronectin binding prior to the addition of rat inflammatory PMNL. The release of both intact and fragmented fibronectin from the 125l-labelled artificial matrix was quantified following the addition of PMNL stimulated by the phagocytosis of opsonized zymosan as well as leukocyte elastase. Stimulated PMNL released three times more radiolabelled fibronectin from the denatured collagen surface during a 4 h incubation as compared with unstimulated PMNL. This pattern of 125I-fibronectin release could also be elicited by the addition of purified leukocyte elastase alone, in the absence of PMNL. The release of radiolabelled fibronectin by stimulated PMNL was blocked in a dose-dependent manner by the addition of both methoxysuccinyl-alanine-alanine-valine chloromethyl ketone (AAPVCK), a leukocyte elastase specific inhibitor as well as phenylmethylsulfonylfluoride (PMSF), a non-specific serine protease inhibitor. Western blot analysis coupled with autoradiography confirmed the presence of fibronectin fragments in the medium after addition of PMNL or leukocyte elastase. The large molecular weight fragments (60–200 kD) were not labelled, but the smaller molecular weight fragments (&lt;45 kD), derived from the artifical matrix, were labelled. Thus, fibronectin complexed with denatured collagen is susceptible to proteolytic degradation by stimulated inflammatory PMNL. Such a process may have a role in the pathogenesis of acute vascular injury following microvascular margination of activated blood leukocytes.
Analysis of the Number and Distribution of Macrophages, Lymphocytes, and Granulocytes in the Mouse Uterus From Implantation Through Parturition
Authors: De Mamata , Wood Gary W 
Published: January 2018

Abstract
The metrial gland and decidua basalis are uterine structures which, during pregnancy in mice and rats, contain bone marrow derived cells. The current study demonstrates that large numbers of bone marrow derived cells, identified by common leukocyte antigen (CLA) positivity, accumulate in the mesometrial uterus between days 6 and 10 and contribute significantly to the cellularity of both the metrial gland and the decidua basalis. The distribution of F4/80+ cells (macrophages) is similar, suggesting that CLA+ cells in the metrial gland and decidua basalis are macrophages. Disappearance of luminal epithelium in the mesometrial uterus between days 11 and 12 leads to regression of metrial gland and decidua basalis and coincident disappearance of CLA+ and F4/80+ cells. A second population of CLA+ and F4/80+ cells appears in association with the development of new uterine luminal epithelium which surrounds the fetus and placenta during the final week of pregnancy. These very large accumulations of macrophages invariably are related to presence of epithelium.
1,25-Dihydroxyvitamin D3 Induces Monocytic Differentiation of the PLB-985 Leukemic Line and Promotes c-fgr mRNA Expression
Authors: Perkins Sherrie L , Link Daniel C , Kling Stephen , Ley Timothy J , Teitelbaum Steven L 
Published: January 2018

Abstract
1,25-dihydroxyvitamin D3 [1,25(OH)2D] is known to stimulate maturation of the human promyelocytic line HL-60 and murine bone marrow precursor cells along a monocyte/macrophage pathway. In this study, the steroid's effects on the PLB-985 leukemic line were examined. We found that 1,25(OH)2D induces monocytic differentiation of PLB-985 as manifested by morphological appearance, histochemical staining, and changes in cell surface antigen expression. Additionally, there was acquisition of functional monocyte characteristics including phagocytic activity and superoxide anion production via the respiratory burst pathway. Steady state levels of mRNA derived from the leukocyte-specific proto-oncogene c-fgr were also increased by the steroid. Thus, 1,25(OH2)D effectively differentiates PLB-985 cells along a monocytic pathway, providing a useful model of macrophage differentiation.
A Cytosolic Inhibitor of Human Neutrophil Elastase and Cathepsin G
Authors: Thomas Raymond M , Nauseef William M , Iyer Shankar S , Peterson Michael W , Stone Phillip J , Clark Robert A 
Published: January 2018

Abstract
The neutrophil serine proteinases elastase and cathepsin G produce connective tissue injury, the extent of which depends on the balance between these enzymes and their inhibitors. The most important of these inhibitors is α1-proteinase inhibitor, a member of a superfamily of homologous proteins known as serpins. Neutrophil cytosol inhibited the activities of human neutrophil elastase and cathepsin G in a dose-dependent fashion. To demonstrate formation of an enzyme-inhibitor complex, we combined 125l-elastase or 125l-cathepsin G with neutrophil cytosol or α1-proteinase inhibitor and analyzed the products by polyacrylamide gel electrophoresis. Unbound elastase and cathepsin G each migrated to an apparent molecular weight of 25 kDa. In the presence of cytosol from neutrophils both radiolabeled enzymes migrated with a relative size of 68 kDa, whereas in the presence of α1-proteinase inhibitor the relative size was 85 kDa. Enzyme-inhibitor complexes were stable in sodium dodecyl sulfate at 100° but were dissociated by hydrolysis in ammonium hydroxide (1.5 mol/L) at 37°. Formation of each complex was prevented by pretreatment of elastase or cathepsin G with diisopropylfluorophosphate, indicating that the inhibitor binds to the active site of the enzyme. Exposure of either α1-proteinase inhibitor or neutrophil cytosol to the myeloperoxidase-H2O2-halide system prevented complex formation, suggesting the presence of an oxidizable amino acid at the binding site of the inhibitor. By electrophoretic analysis, the molecular weight of the cytosolic inhibitor was 43 kDa and neutrophils contained approximately 1 attomol of inhibitor per cell. The isoelectric points of the elastase and cathepsin G inhibitor were 5.5–5.9 and inhibitors of the two proteinases coeluted using size exclusion chromatography. These data demonstrate that human neutrophil cytosol contains a single serpin-like protein that inhibits elastase and cathepsin G. The inhibitor may be important in protecting the intracellular environment from proteolytic injury during degranulation.
Absence of FMLP Receptors on Rat Macrophages
Authors: Walker Blair AM , Seiler Andrew J , Owens Catherine A , Hagenlocker Brian E , Ward Peter A 
Published: January 2018

Abstract
Although rat peritoneal neutrophils in the presence of cytochalasin B demonstrate superoxide (O2-) responses to the chemotactic peptide N'-formyl-met-leu-phe (FMLP), neither elicited rat peritoneal macrophages nor rat alveolar macrophages show an O2-response to FMLP (in the presence or absence of cytochalasin B), although a good O2-response to opsonized zymosan is demonstrated by both types of macrophages. Using Fura-2 loaded cells, peritoneal macrophages failed to show an increase in intracellular calcium after exposure to FMLP, f-nor-leu-phe, F-met-met-met, or F-norleu-leu-phe-norleu-lys. FMLP also failed to induce elevations in intracellular calcium in alveolar macrophages. In 3H-FMLP binding studies, the lack of responsiveness of peritoneal and alveolar macrophages was associated with the lack of FMLP receptors on these cell types, in striking contrast to the presence of functional receptors on rat neutrophils.
Absence of interleukin 1α radioprotection in tumor-bearing animals: elevated plasma levels of prostaglandin E versus a preexisting primed marrow
Authors: Kovacs C J , Harrell J P , Evans M J , Johnke R M 
Published: January 2018

Abstract
Recombinant human interleukin 1 (IL-1) administered as a “priming” agent 24 h prior to hematopoietically lethal doses of total body irradiation (TBI) confers radioprotection to normal G57B1/6 (B6) mice, but not to B6 tumor-bearing animals (TBAs) known to have altered hematopoietic steady states. Using the Lewis lung tumor (LLca) in the B6 mouse, studies were carried out to determine whether the failure of IL-1 to radioprotect the LLca TBA was related to a preexisting “primed” hematopoietic state in the TBA or resulted from inhibition of myelopoietic activity associated with the production of prostaglandin E (PGE) by, or in response to, the tumor. Both normal B6 and LLca B6 TBAs were injected (every 24 h × 1–5) with 100 μg of indomethacin (IND) prior to the administration of IL-1. A single treatment with IND was sufficient to reduce the elevated levels of PGE found in the plasma of the TBAs. After five treatments, IND reduced the PGE level to below that of controls. Neither the acute nor the protracted IND treatment, however, affected the expansion of the stem and progenitor cell compartments of the marrow in the LLca TBA. Furthermore, no evidence of restoration of the radioprotective properties of IL-1 was observed in TBAs pretreated with IND. Collectively, these data suggest that the failure of IL-1 to provide radioprotection to the LLca TBA is not a direct result of the elevated plasma PGE levels associated with growth of the LLca tumor. In addition, these studies provide insight into the importance of examining in vivo effects of biological molecules in altered, as well as normal, physiological states.
Production of tumor necrosis factor α by resident and activated murine macrophages
Authors: Tachibana Katsuyasu , Chen Guan-jie , Huang Dennis S , Scuderi Philip , Watson Ronald Ross 
Published: January 2018

Abstract
Alveolar macrophages (Am⊘s), resident peritoneal macrophages (RPm⊘s), and thioglycolate-elicited peritoneal macrophages (TGPm⊘s) were isolated from C57BL/6 mice and incubated with lipopolysaccharide (LPS), stimulated cell supernatant, or recombinant interferon γ (IFN-γ) for 24 h. Tumor necrosis factor (TNF) in cell-free supernatants was measured by enzyme-linked immunosorbent assay. Anio⊘s incubated with 103 ng/ml LPS produced 50 times more TNF than RPm⊘s and 5 times more than TGPm⊘s, and LPS alone induced maximum TNF production by Am⊘s. Stimulated cell supernatant or recombinant IFN-γ alone did not induce TNF production. A combination of LPS with stimulated cell supernatant or IFN-γ had only a limited synergistic effect on TNF production by Am⊘s. However, both LPS and stimulated cell supernatant or recombinant IFN-γ induced maximum TNF production by RPm⊘s and TGPm⊘s. TGPm⊘s showed greater sensitivity to LPS and stimulated cell supernatant or IFN-γ with regard to TNF production than the other macrophage populations investigated.
Characterization of a direct effect of phorbol myristate acetate on human neutrophil cell membrane using 31D8 monoclonal antibody
Authors: Woronick Charles L , Maderazo Eufronio G , Anthony Monique N , Krause Peter J , Sha'afi Ramadan I 
Published: January 2018

Abstract
We found that 4-β-phorbol 12-myristate 13-acetate (PMA) caused decreased expression of the polymorphonuclear neutrophil (PMN) surface antigen 31D8. In contrast to the rapid initiation of the oxidative burst caused by PMA, the effect was slow to start but increased during incubation periods up to 50 min. To study this apparent protein kinase C-independent late effect of PMA, we measured 31D8 expression in PMNs after incubation with various concentrations of PMA. The maximum PMA-induced inhibition was 76 ± 2%, with an ID50 of 3.9 ± 0.4 ng/ml. Oxidants and prooxidants (hydrogen peroxide, hypochlorite, taurine-chloramine, and ferrous iron, with or without H2O2) had no direct effect on 31D8 antigen expression. The following substances were not protective against the inhibitory affect of PMA: (1) antioxidants (superoxide dismutase, catalase, azide, dimethyl sulfoxide, Desferal, and ascorbate, with the exception of α-tocopherol), (2) inhibitors of protein kinase C (H7 and W7), (3) inhibitors of 5-lipoxygenase (A-63162, MK886, and high-dose indomethacin) and (4) inhibitors of cyclooxygenase (low-dose indomethacin). Myeloperoxidase-deficient PMNs had normal 31D8 antigen expression and a decrease of 31D8 antigen expression by PMA, as did normal PMNs. The inactive analog of PMA, 4-α-phorbol didecanoate, had no effect on 31D8 antigen expression. α-Tocopherol (50 μg/ml) and betamethasone (150 μg/ml) protected against the PMA effect by 30.5 ± 7.3 (P &lt; .0005) and 52 ± 15 (P &lt; 0.004) channels, respectively. These results indicate that PMA has a protein kinase C-independent late effect on human neutrophils, which can be prevented by pretreatment with α-tocopherol or the steroid betamethasone. These compounds probably exert their protective effect by membrane stabilization.