bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphatidylinositol hydrolysis by phospholipase A2 and C activities in human peripheral blood neutrophils
Authors: Smith Duane M , Waite Moseley 
Published: January 2018

Abstract
We describe here and partially characterize a Ca2+-independent phospholipase A2 that acts on phosphatidylinositol in normal human peripheral blood neutrophils. Neutrophils incubated with myo-[3H]inositol to form [3H]phosphatidylinositol and then stimulated with the calcium ionophore A23187 produced [3H]lysophos- phatidylinositol. This deacylation was further characterized in cell sonicates by the specific release of [3H]arachi- donic acid from exogenous [l-14C]stearoyl-2-[3H]arachi- donyl-phosphatidylinositol. This phospholipase A2 is Ca2+ independent, retaining full activity in the presence of 10 mM EDTA, and is optimally active at alkaline pH (pH 9). A phosphatidylinositol-hydrolyzing phospholipase C activity was characterized by the production of [3H]-/[14C]-diglycerides. This phospholipase C activity is dependent on the presence of exogenous Ca2+ and is optimally active at neutral pH (pH 7.5). The lipoxygenase/ cyclooxygenase inhibitors eicosatetrayenoic acid and nor- dihydroguaiaretic acid and the calmodulin antagonist trifluoperazine were the only compounds tested that showed significant inhibition of phospholipase A2 activity. However, none of these phosphatidylinositol-hydrolyzing phospholipase A2 inhibitory compounds resulted in the accumulation of any radiolabeled diglyceride, mono- glyceride, or phosphatidic acid intermediates. Following subcellular fractionation on sucrose density gradients, it was found that the plasma membrane-enriched fractions contained the highest specific activity for phospholipase A2; however, the cytosolic fraction contained a large part of the total phospholipase A2 activity. Furthermore, when neutrophils were first exposed to several agents, including lipopolysaccharide, phorbol myristate acetate, or N-formyl- methionyl-leucyl-phenylalanine, and then subfraction- ated, there was a significant translocation of the enzyme activity from the cytosolic fraction to the membrane- enriched fractions. These data suggest that this Ca2+- independent, phosphatidylinositol-hydrolyzing phospholipase A2 may play an important role in early cell activation, providing free arachidonic acid for subsequent metabolism into biologically active eicosanoids.
Three distinct cell phenotypes of induced-TNF cytotoxicity and their relationship to apoptosis
Authors: Woods Keith M , Chapes Stephen K 
Published: January 2018

Abstract
We have identified three distinct cell phenotypes with respect to the conditions under which cells became susceptible to TNF-mediated lysis. These conditions include: 1) treatment with the protein synthesis inhibitor, cycloheximide; 2) contact with activated macrophages, and 3) infection with vaccinia virus. Whereas vaccinia virus-infected 3T3 cells became sensitive to soluble TNF, F5b cells required contact with activated macrophages. We showed that the “macrophage-resistant” F5m cells did not become sensitive to TNF or to killing by activated macrophages after infection with vaccinia virus. Therefore, vaccinia infection does not sensitize all cells to TNF. We also determined the pathways of lysis for cells after sensitization. Whereas 3T3, LM929, and F5b cells were killed by the process of necrosis, F5m cells lysis was characterized by the release of low mol wt DNA fragments (apoptosis). J. Leukoc. Biol. 53: 37–44; 1993.
Selective refractoriness of macrophages to endotoxin-induced production of tumor necrosis factor, elicited by an autocrine mechanism
Authors: Fahmi Hassan , Chaby Richard 
Published: January 2018

Abstract
Tolerance of macrophages to endotoxin (lipopolysaccharide, LPS) can be induced in vitro by LPS itself. We show here that one of the mechanisms of tolerance to LPS can be mediated via an autocrine process. Continuous exposure to LPS is not required to induce macrophage desensitization. Refractoriness to production of tumor necrosis factor (TNF) in response to LPS can be transferred from tolerant to naive macrophage populations by incubation of the latter with the culture supernatant of the former, in the absence of endotoxin. The active factor present in this macrophage-desensitizing culture supernatant (MD-Sup) is more efficiently removed by incubation with tolerant macrophages than by incubation with naive macrophages. The refractoriness elicited by treatment with MD-Sup is restricted to a decreased TNF response to LPS; interleukin-1 (IL-1) and IL-6 responses are not affected. J. Leukoc. Biol. 53: 45-52; 1993.
Inhibition of Corynebacterium parvum–primed and lipopolysaccharide-induced hepatic necrosis in rats by selective depletion of neutrophils using a monoclonal antibody
Authors: Sato Tsukasa , Shinzawa Haruhide , Abe Yoshihiro , Takahashi Tsuneo , Arai Shigeru , Sendo Fujiro 
Published: January 2018

Abstract
To examine whether neutrophils are involved in the pathogenesis of experimental liver dysfunction, we observed the effect of selective in vivo neutrophil depletion by a monoclonal antibody (RP-3) on the pathogenesis of acute experimental hepatic necrosis in rats induced by a preparative injection of heat-killed Corynebacterium parvum and a challenging dose of lipopolysaccharide (LPS) (positive control group). The serum transaminase titer 8 h after LPS injection was reduced by selective depletion of peripheral blood neutrophils as a result of RP-3 treatment (RP-3 group). A kinetic study showed that the serum transaminase titer of the RP-3 group was significantly lower than that of the positive control group from 4 to 24 h after LPS injection. The transaminase level was significantly lower in the group with less than 400/mm3 peripheral blood neutrophils than in the group with a greater number. The effect of RP-3 on the transaminase level was due neither to the injection of cancer ascites nor to RP-3 injection with the accompanying decrease in complement titer. These results suggest that neutrophils play an important role in the induction of liver dysfunction in this system. J. Leukoc. Biol. 53: 144–150; 1993.
Isolation of a human endothelial cell C1q receptor (C1qR)
Authors: Peerschke Ellinor IB , Malhotra Rajneesh , Ghebrehiwet Berhane , Reid Kenneth BM , Willis Anthony C , Sim Robert B 
Published: January 2018

Abstract
Clq binding to endothelial cells has been described previously, but the putative cell surface receptor (s) has not been identified. In the present study, modifications of a reported purification of lymphocyte Clq receptor (ClqR) were used to isolate Clq binding sites from human umbilical vein endothelial cells. Cells were harvested, without protease treatment, at passage 10-17 and lysed with 1% Triton X-100. The lysate was fractionated on Fast-performance liquid chromatography (FPLC) Mono-Q using a linear NaCl gradient, followed by high-performance liquid chromatography (HPLC) ion exchange (TSKgel DEAE-NPR). A major protein was eluted that had the same mobility on sodium dodecyl sulfate-polyacrylamide gels and the same NHHerminal sequence as lymphocyte ClqR. This protein was expressed on the surface, as judged by surface radioiodination, bound to Clq-coated surfaces, and was recognized by polyclonal antilymphocyte ClqR antibodies. Thus, endothelial cells express a Clq receptor that appears identical to lymphocyte ClqR. The data further support the hypothesis that cell surface ClqRs identified on a variety of somatic and cultured cells are either identical or constitute a family of closely related molecules. J. Leukoc. Biol. 53: 179–184; 1993.
Interleukin-1-dependent mitogenic responses induced by protoscoleces of Echinococcus multilocularis in mur ine lymphocytes
Authors: Kizaki Takako , Ishige Masamichi , Bingyan Wang , Kumagai Mitsuru , Day Noorbibi K , Good Robert A , Onoé Kazunori 
Published: January 2018

Abstract
Mitogenic effects of protoscoleces (PSCs) of Echinococcus multilocularis on murine lymphocytes were studied. Spleen cells from normal BALB/c mice showed significant proliferative responses when cocultured with PSCs. Proliferative responses were observed in both the T and B cell populations. The PSCs also stimulated cells of the macrophage/monocyte lineage to secrete inter-leukin-1 (IL-1). Depletion of plastic- and Sephadex G-10-adherent cells from the spleen cell population significant-ly reduced the proliferative responses to PSCs and the low responsiveness was restored by addition of plastic-ad-herent cells to these cultures. Furthermore, addition of anti-lL-l serum to the spleen cell cultures stimulated with PSCs completely suppressed the proliferative responses. These findings demonstrate that the mitogenic effect of PSC on lymphocytes depends on EL-1 secreted by cells of macrophage/monocyte lineage. J. Leukoc. Biol. 53: 233–239; 1993.
Laminin cleavage by activated human neutrophils yields proteolytic fragments with selective migratory properties
Authors: Steadman Robert , Irwin Michael H , John Patricia L St , Blackburn Warren D , Heck. Louis W , Abrahamson Dale R 
Published: January 2018

Abstract
We studied the interactions between human neutrophils, as well as the purified human neutrophil serine proteases elastase (HNE) and cathepsin G (HNCG), and laminin. Our results show that intact laminin and two proteolytic fragments generated by HNE bind to neutrophils and stimulate cell migration. Domain- specific antilaminin monoclonal antibodies, rotary shadowing electron microscopy, and Western blotting mapped the two promigratory fragments on the laminin cross to the apical three-armed region and long arm, respectively. In contrast, a fragment derived from the terminal ends of short arms neither bound to neutrophils nor stimulated migration. When neutrophils embedded in a reconstituted basement membrane gel were activated with phorbol myristate acetate, several stable, proteolytic laminin fragments were released into supernatants. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting showed that these fragments appeared identical to those generated after digestion of soluble laminin with HNE and HNCG. Furthermore, release of laminin fragments by embedded neutrophils was inhibited by diisopropyl fluorophos- phate, and duplicated by incubating the basement membrane gel with purified HNE and HNCG. Our findings therefore suggest that neutrophils, through release of HNE and HNCG, are capable of digesting basement membrane laminin in vivo. In addition, the release of laminin fragments from damaged basement membranes may promote neutrophil migration and thereby accelerate inflammatory processes. J. Leukoc. Biol. 53: 354–365; 1993.
Nitric oxide synthase inhibitors attenuate human monocyte chemotaxis in vitro
Authors: Belenky Sergei N , Robbins Richard A , Rubinstein Israel 
Published: January 2018

Abstract
Nitric oxide synthase (NOS) inhibitors have been shown to modulate neutrophil migration. We hypothesized that the NOS inhibitors NG-monomethyl-L- arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME), and L-canavanine (L-CAN) also modulate human peripheral blood monocyte chemotaxis. To test this hypothesis, monocyte chemotaxis toward formylmethionyl- leucyl-phenylalanine (fMLP) was assessed using a modified blindwell chemotaxis chamber technique. L- NMMA and L-NAME, but not D-NMMA or L-CAN, significantly attenuated fMLP-induced monocyte chemotaxis (P &lt; .05). L-Arginine and sodium nitroprusside, but not D-arginine, reversed NOS inhibitor-induced responses. Dibutryl cyclic guanyl monophosphate (cGMP) attenuated the inhibitory effects of L-NMMA on monocyte chemotaxis (P &lt; .05). Finally, fMLP increased cGMP generation by monocytes, which was significantly attenuated by L-NMMA (P &lt; .05). These data indicate that the L-arginine/NO biosynthetic pathway regulates human monocyte chemotaxis in vitro. J. Leukoc. Biol. 53: 498–503; 1993.
Tumor growth increases la− macrophage synthesis of tumor necrosis factor-α and prostaglandin E2: changes in macrophage suppressor activity
Authors: Alieva David G , Burger Carol J , Elgert Klaus D 
Published: January 2018

Abstract
Although tumor growth enhances macrophage (mφ) cytotoxic activity by increasing their tumor necrosis factor-a (TNF-a) production, increased prostaglandin E2 (PGE2) synthesis reduces most immune responses during tumor growth. Macrophages that do not express major histocompatibility complex class II molecules (la− mφ) are the predominant suppressor and cytotoxic population and are more abundant in tumor-bearing hosts (TBHs). This study determined if TBH la’ mφs are the major population producing TNF-α and PGE2 and if these molecules affect la’ mφ-mediated suppression of alloantigen-stimulated T cell proliferation. Normal host (NH) and TBH splenic Ia+-depleted (la−) mφs synthesized more TNF-a than their respective whole populations (WPs) when cultured with lipopolysaccharide and interferon-7. TBH la’ mφs produced the most TNF-α. Northern blot analyses showed that la’ mφs had higher amounts of TNF-α mRNA expression than their respective WP, and TBH la” mφs expressed the highest amounts of TNF-α mRNA. When WP and la’ NH and TBH mφs were added to alloantigen-stimulated T cells, suppression of T cell proliferation mediated by la’ mφs was greater than by their respective WP. TBH Ia− mφs were most suppressive. The blockage of PGE2 production reduced suppression mediated by TBH la” mφs more than by all other mφ populations. A PGE2-specific enzyme-linked immunosorbent assay showed that PGE2 production was greater in la’ mφ- than in WP mφ-containing cultures and greatest in cultures containing TBH la’ mφs. Because TNF-α enhances T cell responses, its effects on la−mφ PGE2-mediated suppression was determined. When TNF- a was added to mφ-containing T cell cultures, TNF-α directly stimulated NH, but not TBH, la’ mφs, which enhanced T cell proliferation. However, inhibiting PGE2 production allowed TNF-a to stimulate T cell proliferation in TBH la” mφ-containing cultures. Collectively, these data show that la’ mφs are the major TNF-α- and PGE2-producing cells and that these molecules are partly responsible for the tumor-induced increase in mφ- mediated cytotoxicity and suppression, respectively. TNFα not only mediates cytotoxicity but also counteracts la− mφ PGE2-mediated suppression. Although tumor growth increases la’ mφ TNF-α production, enhanced PGE2 production blocks TNF-α’s stimulatory action on la− mφs, which favors their suppressor function during tumor growth. J. Leukoc. Biol. 53: 550–558; 1993.
Effects of inhibition of lipoxygenase and guanylate cyclase on human neutrophil responses to formyl peptide and granulocyte-macrophage colony-stimulating factor
Authors: Coffey Ronald G , Diaz Sharon , Coffey Christina S 
Published: January 2018

Abstract
Human neutrophils were activated by the bacterial chemotactic peptide N-formylmethionyl-leucyl- phenylalanine (fMLP) to produce superoxide (O2”) and to release the primary granule enzyme β-glucuronidase and the predominantly secondary granule enzyme lysozyme. Pretreatment with granulocyte-macrophage colony- stimulating factor (GM-CSF) increased the secretion of all three substances upon addition of fMLP. The augmentation by GM-CSF was significantly attenuated by the 5-lipoxygenase inhibitor AA861 and by the guanylate cyclase inhibitor LY83583. The secretion induced by fMLP alone was much less affected by either of the two inhibitors. AA861 inhibited leukotriene B4 production in neutrophils primed with GM-CSF and stimulated with fMLP, and LY83583 inhibited GM-CSF-evoked increases of 3′,5′-guanosine monophosphate. The data suggest that activation of lipoxygenase and guanylate cyclase is not critical to the fMLP stimulation pathway, but they may be important components of the pathway by which GM-CSF augments neutrophil responses to fMLP. However, AA861 and LY83583 may have important actions in addition to inhibition of 5-lipoxygenase and guanylate cyclase.
Overview of spaceflight immunology studies
Authors: Taylor Gerald R 
Published: January 2018

Abstract
The effects of spaceflight and analogues of spaceflight are discussed here and in nine accompanying articles. In this summary we present spaceflight studies with human subjects, animal subjects, and cell cultures and we review ground-based systems used to model the observed effects of spaceflight on the immune system. Human paradigms include bed rest, academic or psychological stress, physical stress, hypobaric or high altitude stress, and confinement. Animal models include antior- thostatic and orthostatic suspension, hypobarism, and confinement. The ten manuscripts in this collection were selected to provide a summary that should give the reader an overview of the various activities of spaceflight immunology researchers throughout the history of space travel. This manuscript identifies the major contributors to the study of spaceflight immunology, explains what types of studies have been conducted, and how they have changed over the years. Also presented is a discussion of the unusual limitations associated with spaceflight research and the efforts to develop appropriate ground-based surrogate model systems. Specific details, data, and mechanistic speculations will be held to a minimum, because they will be discussed in depth in the other articles in the collection.
The role of cytokines in immune changes induced by spaceflight
Authors: Sonnenfeld Gerald , Miller Edwin S 
Published: January 2018

Abstract
It has become apparent that spaceflight alters many immune responses. Among the regulatory components of the immune response that have been shown to be affected by spaceflight is the cytokine network. Spaceflight, as well as model systems of spaceflight, have been shown to affect the production and action of various cytokines including interferons, interleukins, colony stimulating factors, and tumor necrosis factors. These changes have been shown not to involve a general shutdown of the cytokine network but, rather, to involve selective alterations of specific cytokine functions by spaceflight. The full breadth of changes in cytokines in- duced by spaceflight, as well as mechanisms, duration, adaptation, reversibility, and significance to resistance to infection and neoplastic diseases, remains to be established.
Granulocytes enhance LPS-induced tissue factor activity in monocytes via an interaction with platelets
Authors: Halvorsen Hanne , Olsen Jan Ole , Osterud Bjarne 
Published: January 2018

Abstract
In the present study we have investigated the effect of platelets and granulocytes on bacterial lipopoly- saccharide (LPS)-induced tissue factor (TF) activity in monocytes. Experiments were performed on freshly isolated cells resuspended in heparinized plasma and recombined with platelet-poor or platelet-rich plasma. In a platelet-dependent reaction the granulocytes enhanced LPS-induced TF activity by an average of 100%. The effect was dose dependent with regard to the number of both granulocytes and platelets, respectively. Granulocytes and/or platelets did not affect LPS-induced tumor necrosis factor (TNF) secretion from monocytes. Phorbol myristate acetate (PMA) per se was not able to induce TF activity in our system. In contrast, the agonist caused a substantial increase in TF activity induced by LPS. The effect was totally dependent on the presence of platelets and was shown to be due to stimulation of both granulocytes and monocytes (the activity rose from 30 ± 7 to 83 ± 12 mU/106 cells in the presence of platelets and from 69 ± 8 to 143 ± 22 mU/106 cells in the presence of platelets and granulocytes). Effects similar to those observed with PMA were obtained with physiological concentrations (10 ng/ml) of TNF. A combination of these two agonists gave no further amplification of LPS-induced TF activity compared with the effect of the agonists separately. Low concentrations of a monoclonal anti- CD15 antibody abolished the stimulatory effects of platelets and granulocytes. Furthermore, the anti-GDI 5 antibody neutralized the effect of TNF, whereas the PMA effect was reduced by almost 75%. These results were confirmed in a whole-blood system. The inhibitory effect of the antibody may be associated with CD15’s role as a complementary ligand for PADGEM. Our study indicates that a close interaction between granulocytes, platelets, and monocytes is essential for optimal TF activity induced by LPS. It is hypothesized that the effect of granulocytes is related to their ability to activate platelets. We propose that upon activation granulocytes secrete a product that enhances the capacity of platelets to stimulate TF activity in monocytes.
Effect of lipoxins and other eicosanoids on phagocytosis and intracellular calcium mobilisation in rainbow trout (Oncorhynchus mykiss) leukocytes
Authors: Knight J , Lloyd-Evans R , Rowley A F , Barrow S E 
Published: January 2018

Abstract
Rainbow trout (Oncorhynchus mykiss) macrophages generated lipoxin (LX) A4, LXA5, leukotriene (LT) B4, LTB5 and 12-hydroxyeicosatetraenoic acid (12-HETE) during the phagocytosis of zymosan and Escherichia coli, but not of the yeast Saccharomyces cerevisiae. Prostaglandin (PG) E2 was also detected in supernatants from macrophages incubated with either zymosan or calcium ionophore A23187. LXA4 (10−8- 10−6 M) and LTB4 (10−9-10−7 M) provoked rapid and transient dose-dependent increases in intracellular calcium ([Ca]i) concentrations in leukocyte suspensions containing 40-60% macrophages. EC50 values were 14.9 and 1.2 nM, respectively. PGE2 and 12-HETE had no effect on [Ca]i at concentrations up to 30 μM. PGE2 and 12-HETE (10−5-10−10 M) enhanced the in vitro phagocytosis of yeast test particles by trout macrophages, whereas LXA4 and LTB4 had no demonstrable effect on the responses of these cells at concentrations up to 10−5 M. In conclusion, the processes involved in trout macrophage stimulation are complex but involve generation of both cyclooxygenase and lipoxygenase products. The increase in [Ca]i caused by LXA4 and LTB4 may form part of the chemotactic transduction mechanism that recruits granulocytes and macrophages to sites of inflammation. The effects of eicosanoids on phagocytosis appear to be independent of changes in [Ca]i.