bluuebunny/crossref_metadata_2025_split huggingface dataset:
Priming effects of substance P on calcium changes evoked by interleukin-8 in human neutrophils
Authors: Dianzani Chiara , Lombardi Grazia , Collino Massimo , Ferrara Cinzia , Cassone Maria Chiara , Fantozzi Roberto 
Published: September 2022

AbstractThe neurokinin (NK) substance P (SP), which is a mediator of neurogenic inflammation, has been reported to prime human polymorphonuclear neutrophils (PMNs). The priming effects of SP on PMNs activated by recombinant interleukin-8 (rIL-8) were investigated. SP enhanced, in a dose- and time-dependent way, the rise in cytosolic free-calcium concentration, [Ca2+]i, evoked by the chemokine. The priming effects of SP were abolished by exposing PMNs to a calcium-free medium supplemented with EGTA. The C-terminal peptides SP(4–11) and SP(6–11) but not the N-terminal peptide SP(1–7) shared the priming effects of SP. The selective NK-1 receptor agonist [Sar-9, Met(O)2-11]SP mimicked the effects of SP, which were not reproduced by the selective NK-2 receptor agonist [βAla-8]-NKA(4–10) or the selective NK-3 agonist senktide. Two selective NK-1 antagonists, CP96,345 and L703,606, dose dependently inhibited SP priming effects. These results demonstrated that SP primes PMNs exposed to rIL-8 and suggested that SP priming effects are receptor mediated.
Retardation of early-onset PMA-induced apoptosis in mouse neutrophils deficient in myeloperoxidase
Authors: Tsurubuchi Tetsuto , Aratani Yasuaki , Maeda Nobuyo , Koyama Hideki 
Published: September 2022

AbstractNeutrophil apoptosis is a mechanism involved in the resolution of inflammation. To explore the role of hypochlorous acid (HOCl) produced by neutrophils while they are undergoing apoptosis, we compared the rates of apoptosis in neutrophils isolated from normal mice and from myeloperoxidase (MPO)-deficient mice, which are unable to generate HOCl. Apoptosis in MPO-deficient neutrophils stimulated by phorbol myristate acetate (PMA) was significantly slower than in normal neutrophils during 3 h of incubation. Exposure of normal neutrophils to H2O2 together with PMA resulted in a dramatic acceleration of apoptosis, and almost all of the cells revealed apoptotic morphology at 1 h. This acceleration was inhibited by cytochrome c, a superoxide scavenger. Conversely, in MPO-deficient neutrophils activated with PMA and H2O2, little acceleration was observed before 1 h, although it gradually increased thereafter. This retardation was almost completely reversed when MPO or HOCl was exogenously added. These results suggest that coexistence of HOCl and superoxide accelerates the early onset of neutrophil apoptosis.
Nitric oxide induces murine thymocyte apoptosis by oxidative injury and a p53-dependent mechanism
Authors: Gordon Sherilyn A , Abou-Jaoude Walid , Hoffman Rosemary A , McCarthy Susan A , Kim Young-Myeong , Zhou Xin , Zhang Xiao-Ru , Simmons Richard L , Chen Yue , Schall Laura , Ford Henri R 
Published: September 2022

AbstractPreviously, we showed that NO induces thymocyte apoptosis via acaspase-1-dependent mechanism [1]. In the present study,we investigated the role of heme oxygenase, catalase, bax, and p53 inthis process. The NO donor, S-nitroso-N-acetyl penicillamine (SNAP),induced DNA fragmentation in thymocytes in a time- andconcentration-dependent way. SNAP (100 μM) induced 50–60%apoptosis; higher doses did not increase the rate of apoptosissignificantly. SNAP decreased catalase and heme iron (Fe) levelswithout affecting superoxide dismutase, glutathione, or total Fe storesin thymocytes. SNAP significantly increased the expression of hemeoxygenase 1 (HSP-32), p53, and bax but notbcl-2. Treatment with the heme oxygenase inhibitor, tinprotoporphyrin IX inhibited SNAP-induced thymocyte apoptosis.Furthermore, thymocytes from p53 null mice were resistantto NO-induced apoptosis. Our data suggest that NO may induce itscytotoxic effects on thymocytes by modulating heme oxygenase andcatalase activity as well as up-regulating pro-apoptotic proteinsp53 and bax.
Functional heterogeneity in liver and lung macrophages
Authors: Laskin Debra L , Weinberger Barry , Laskin Jeffrey D 
Published: September 2022

AbstractAlthough initially considered merely “scavenger cells” that participate in immunologic responses only after B and T lymphocytes have performed their biological tasks, more recent evidence suggests that macrophages play a key role in host defense as well as in the maintenance of normal tissue structure and function. For macrophages to perform their biological functions, they must be activated. This involves up-regulation of an array of signaling pathways resulting in altered gene expression and increased biochemical and functional activity. Macrophages have been identified in almost all tissues of the body. However, the basal activity of these cells, as well as their ability to respond to inflammatory mediators, varies considerably with their location. In addition, even within a particular tissue, there is evidence of macrophage heterogeneity. The largest populations of macrophages in the body are located in the liver and lung. Because of the unique attributes of these tissues, hepatic and pulmonary macrophages play essential roles not only in nonspecific host defense but also in the homeostatic responses of these tissues. In this review, the functional and biochemical activities of macrophages localized in the liver and lungs are compared. Evidence suggests that these represent distinct cell populations with unique functions and responsiveness to inflammatory agents.
Effects of hypertonic saline on expression of human polymorphonuclear leukocyte adhesion molecules
Authors: Thiel M , Buessecker F , Eberhardt K , Chouker A , Setzer F , Kreimeier U , Arfors K-E , Peter K , Messmer K 
Published: September 2022

AbstractHypertonic saline prevents vascular adherence of neutrophils and ameliorates ischemic tissue injury. We hypothesized that hypertonic saline attenuatesN-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated expression of adhesion molecules on human polymorphonuclear leukocytes (PMNLs). fMLP-stimulated up-regulation of β2-integrins was diminished by hypertonic saline but not by hypertonic choline chloride-, mannitol-, or sucrose-modified Hanks’ buffered salt solution. Shedding of l-selectin was decreased by hypertonic saline and choline chloride but not by hypertonic mannitol or sucrose. When the effects of hypertonic sodium chloride- and choline chloride-modified media were compared, neither solution affected fMLP-receptor binding but both equally inhibited fMLP-stimulated increase in intracellular calcium, ionophore A23187, and phorbol myristate acetate (PMA)-stimulated numerical up-regulation of β2-integrins. Analysis of mitogen-activated protein (MAP) kinases p38 and p44/42 for phosphorylation revealed that hypertonic solutions did not differ in preventing fMLP-stimulated increases in phospho-p38 and phospho-p44/42. Resting PMNLs shrunk by hypertonic saline increased their volume during incubation and further during chemotactic stimulation. Addition of amiloride further enhanced inhibition of up-regulation of β2-integrins. No fMLP-stimulated volume changes occurred in PMNLs exposed to hypertonic choline chloride, resulting in significant cell shrinkage. Results suggest a sodium-specific inhibitory effect on up-regulation of β2-integrins of fMLP-stimulated PMNLs, which is unlikely to be caused by alterations of fMLP receptor binding, decrease in cytosolic calcium, attenuation of calcium or protein kinase C-dependent pathways, suppression of p38- or p44/42 MAP kinase-dependent pathways, or cellular ability to increase or decrease volumes.
Contributions ofNeisseria meningitidisLPS and non-LPS to proinflammatory cytokine response
Authors: Sprong Tom , Stikkelbroeck Nike , van der Ley Peter , Steeghs Liana , van Alphen Loek , Klein Nigel , Netea Mihai G , van der Meer Jos W M , van Deuren Marcel 
Published: September 2022

AbstractTo determine the relative contribution of lipopolysaccharide (LPS) and non-LPS components of Neisseria meningitidis to the pathogenesis of meningococcal sepsis, this study quantitatively compared cytokine induction by isolated LPS, wild-type serogroup B meningococci (strain H44/76), and LPS-deficient mutant meningococci (strain H44/76[pLAK33]). Stimulation of human peripheral-blood mononuclear cells with wild-type and LPS-deficient meningococci showed that non-LPS components of meningococci are responsible for a substantial part of tumor necrosis factor (TNF)-α and interleukin (IL)-1β production and virtually all interferon (IFN)-γ production. Based on tricine sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of LPS in proteinase K-treated lysates of N. meningitidis H44/76, a quantitative comparison was made between the cytokine-inducing capacity of isolated and purified LPS and LPS-containing meningococci. At concentrations of &gt;107 bacteria/mL, intact bacteria were more potent cytokine inductors than equivalent amounts of isolated LPS, and cytokine induction by non-LPS components was additive to that by LPS. Experiments with mice showed that non-LPS components of meningococci were able to induce cytokine production and mortality. The principal conclusion is that non-LPS parts of N. meningitidis may play a role in the pathogenesis of meningococcal sepsis by inducing substantial TNF-α, IL-1β, and IFN-γ production.
Augmented TNF-α and IL-10 production by primed human monocytes following interaction with oxidatively modified autologous erythrocytes
Authors: Liese Amy M , Siddiqi Muhammad Q , Siegel John H , Denny Thomas , Spolarics Zoltán 
Published: September 2022

AbstractThe presence of dysfunctional/damaged red blood cells (RBCs) has been associated with adverse clinical effects during the inflammatory response. The aim of this study was to elucidate whether oxidatively modified, autologous RBCs modulate monocyte cytokine responses in humans. Monocyte tumor necrosis factor α (TNF-α) and IL-10 production was measured in whole blood from healthy volunteers using ELISA and flow cytometry. Oxidatively modified RBCs (15 mM phenylhydrazine, 1 h, OX-RBC) or vehicle-treated RBCs (VT-RBC) opsonized by autologous serum were administered alone or in combination with one of three priming agents: E. coli lipopolysaccharide (LPS, 0.2 ng/ml), zymosan A (1 mg/ml), or phorbol 12-myristate 13-acetate (PMA, 50 ng/ml). OX-RBC or VT-RBC alone did not result in the release of TNF-α or IL-10. LPS, zymosan, and PMA caused marked and dose-dependent increases in TNF-α and IL-10 production. Addition of OX-RBC augmented the LPS-, zymosan-, and PMA-induced TNF-α release by approximately 100%. OX-RBC augmented LPS- and zymosan-induced IL-10 release by 400–600%. Flow cytometry analyses showed that monocytes were responsible for TNF-α and IL-10 production in whole blood. The presence of OX-RBC alone increased the complexity of CD14+ monocytes but caused no cytokine production. LPS alone induced cytokine production without altering cell complexity. After the combined (OX-RBC+LPS) treatment, monocytes of high complexity were responsible for TNF-α production. The presence of mannose or galactose (at 10–50 mM) did not alter the observed augmentation of cytokine production by OX-RBC, suggesting that lectin receptors are not involved in the response. These studies indicate that the interaction between damaged autologous erythrocytes and monocytes has a major impact on the cytokine responses in humans. An augmented cytokine production by the mononuclear phagocyte system may adversely affect the clinical course of injury and infections especially in genetic or acquired RBC diseases or after transfusions.
A novel bioactive 31-amino acid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes
Authors: Cui Ping , Tani Kenji , Kitamura Hiroko , Okumura Yuushi , Yano Mihiro , Inui Daisuke , Tamaki Toshiaki , Sone Saburo , Kido Hiroshi 
Published: September 2022

AbstractEndothelin (ET)-1(1-31) is a novel 31-amino acid-length peptide derived from big ET-1 by chymase or other chymotrypsin-type proteases and is a major ET derivative in human neutrophils. In this study, we revealed that ET-1(1-31), but not big ET, exhibited chemotactic activities toward human neutrophils and monocytes as an inflammatory mediator, although the effects were less potent than those of formyl-methionyl-leucyl-phenylalanine or interleukin-8. However, the chemotactic effects of ET-1(1-31) were much greater than those of the 21-amino acid ET-1, ET-1(1-21). Checkerboard analyses revealed that the effects are chemotactic rather than chemokinetic. The effects of ET-1(1-31) are not mediated by interleukin-8 or monocyte chemoattractant protein-1. The chemotactic effects and an increase in intracellular-free Ca2+ caused by ET-1(1-31) were significantly inhibited by BQ123, an ETA receptor antagonist, but not by BQ788, an ETB receptor antagonist, suggesting that ET-1(1-31) mediates chemotaxis through an ETA or ETA-like receptor.
A small-molecule antagonist of LFA-1 blocks a conformational change important for LFA-1 function
Authors: Woska Joseph R , Shih Daw-tsun , Taqueti Viviany R , Hogg Nancy , Kelly Terence A , Kishimoto Takashi K 
Published: September 2022

AbstractLymphocyte function-associated antigen(LFA)-1/intercellular adhesion molecule (ICAM)-1interactions mediate several important steps in the evolution of animmune response. LFA-1 is normally expressed in a quiescent state onthe surface of leukocytes and interacts weakly with its ligands ICAM-1,-2, and -3. LFA-1 activity may be regulated by receptor clustering andby increasing the affinity of LFA-1 for its ligands. Affinitymodulation of LFA-1 has been shown to occur via a conformational changein the LFA-1 heterodimer that can be detected by using monoclonalantibody 24 (mAb24). We have recently described a small-moleculeantagonist of LFA-1, BIRT 377, that demonstrates selective in vitro andin vivo inhibition of LFA-1/ICAM-1-mediated binding events. We nowdemonstrate that BIRT 377 blocks the induction of the mAb24 reporterepitope on LFA-1 on the surface of SKW-3 cells treated with variousagonists known to induce high-affinity LFA-1. These data imply thatBIRT 377 exerts its inhibitory effects by preventing up-regulation ofLFA-1 to its high-affinity conformation.
Hemofiltrate CC chemokines with unique biochemical properties: HCC-1/CCL14a and HCC-2/CCL15
Authors: Forssmann Ulf , Mägert Hans-Jürgen , Adermann Knut , Escher Sylvia E , Forssmann Wolf-Georg 
Published: September 2022

AbstractThe hemofiltrate CC chemokines CCL14a (formerly HCC-1), CCL14b (formerly HCC-3), and CCL15 (formerly HCC-2) are encoded by mono- as well as bicistronic transcripts from a tandem gene arrangement on human chromosome 17q11.2. The transcription and splicing into several mono- and bicistronic transcripts of this gene complex are unique for human genes. No corresponding mechanism is known in nonprimate mammalian species such as mice and rats. The extremely high concentration of CCL14a in human plasma is exceptional for chemokines and led to the identification of this chemokine. Several molecular forms of CCL14a have been isolated and investigated. The mature propeptide CCL14a(1–74) is a low-affinity agonist of CCR1 which is converted to a high-affinity agonist of CCR1 and CCR5 on proteolytic processing by serine proteases. In contrast, CCL15 is characterized using molecular forms deduced from the mRNA/cDNA and shown to activate cells via CCR1 and CCR3, also dependent on the amino-terminal length. Hemofiltrate CC chemokines are chemoattractants for different types of leukocytes including monocytes, eosinophils, T cells, dendritic cells, and neutrophils. In this review, we emphasize the genomic organization, expression patterns, and biochemical properties of CCL14a, CCL14b, and CCL15. We report results of significance for the development of therapeutic strategies, especially concerning HIV infection and inflammatory diseases.
Interleukin-12 increases interleukin 8 production and release by human polymorphonuclear neutrophils
Authors: Ethuin Frédéric , Delarche Charlotte , Benslama Sylvie , Gougerot-Pocidalo Marie-Anne , Jacob Laurent , Chollet-Martin Sylvie 
Published: September 2022

AbstractInterleukin (IL) 12 is a heterodimeric cytokine mainly produced by phagocytes—important target cells for IL-12 in particular with a chemotactic effect—and antigen-presenting cells in response to various microorganisms. Because IL-8 is a strong chemokine for polymorphonuclear neutrophils (PMNs), we investigated the effect of IL-12 on PMN IL-8 production. IL-12 alone had no significant effect, but with lipopolysaccharide (LPS) it was additive at both protein and mRNA levels. Actinomycin D at the beginning of culture inhibited IL-8 mRNA induction, whereas late addition affected IL-8 transcript stability, suggesting gene transcription involvement. Results with parthenolide and tyrphostin AG490 suggest that nuclear factor-κB and signal transducer and activator of transcription 4 play a role. The IL-12 additive effect was restricted to IL-8 release, with no action on cell-associated IL-8. IL-12 additive effects occurred after 18 h of culture, with no marked up-regulation of IL-12 receptor expression, and were blocked by actinomycin D added after 16 h of culture. Tumor necrosis factor (TNF) α and interferon (IFN) γ had intermediate roles; their specific inhibition reduced IL-12'SSSs effect. IL-12's chemotactic mechanism seemed mediated by overproduction and release of IL-8 by human PMNs in the presence of LPS, an effect involving TNF-α and IFN-γ secretion. These results point to a new role for IL-12 in inflammation, through an autocrine amplification loop.
Microenvironmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors
Authors: Crowther M , Brown N J , Bishop E T , Lewis C E 
Published: September 2022

AbstractAngiogenesis is the development of blood vessels from an existing vasculature. This process is fundamental to both physiological wound healing and the growth of malignant tumors, as it restores or creates a blood supply to growing tissue. In both cases, the release of angiogenic molecules by macrophages recruited to the wound or tumor site is central to the formation of these neovessels. Reduced vascular perfusion in tissues generates tissue ischemia and a marked reduction in local levels of oxygen (hypoxia) and glucose. Cells adapt by switching to anaerobic metabolic pathways, with a concomitant increase in lactate production and reduction in extracellular pH. In tumors, these microenvironmental “stress” factors stimulate tumor cells to secrete a wide array of proangiogenic cytokines and enzymes, promoting the re-establishment of a local vascular supply. Here we review the evidence that these stress factors, in particular hypoxia and high lactate levels, stimulate macrophages to perform similar proangiogenic functions in both tumors and wounds. The resolution of wounds results in restoration of tissue integrity and perfusion, and macrophage presence is reduced to preinjury levels. However, in tumors a high number of macrophages persists and might contribute to the ongoing growth, neovascularization, and metastasis of malignant cells.
Spontaneous formation of germinal centers in autoimmune mice
Authors: Luzina Irina G , Atamas Sergei P , Storrer Catherine E , daSilva Ludmila C , Kelsoe Garnett , Papadimitriou John C , Handwerger Barry S 
Published: September 2022

AbstractThe mechanisms of autoantibody production are not well understood. Germinal centers (GC) may be important sites of immune disregulation in autoimmune diseases. In this study, we document the presence of spontaneous GC formation in the spleens of several autoimmune mouse strains that spontaneously develop autoimmune Type I diabetes and a lupus-like disease. In contrast, mouse strains that do not develop lupus did not exhibit spontaneous formation of GC. In all of the autoimmune strains studied, GC were present at 1–2 months of age, a time that closely parallels the appearance of autoantibodies. Like the GC that develop after purposeful immunization, GC in autoimmune mice contained B220+, PNA+, and GL-7+ B cells, and FDC-M1+ follicular dendritic cells. In addition, spontaneously formed GC in autoimmunity and those caused by immunization were abrogated in a similar way by a short-term treatment with anti-CD40 ligand antibody. These data indicate that spontaneously forming GC in autoimmunity are similar to those appearing after purposeful immunization.
Involvement of p38-mitogen-activated protein kinase in staphylococcus aureus-induced neutrophil apoptosis
Authors: Lundqvist-Gustafsson Helen , Norrman Sara , Nilsson Jessica , Wilsson Åsa 
Published: September 2022

AbstractApoptosis occurred in human neutrophils within an hour of exposure to viable serum-opsonized Staphylococcus aureus, as indicated by appearance of cells with condensed nuclei, fragmented DNA, and increased phosphatidylserine exposure. In contrast, serum-opsonized, heat-killed S. aureus did not induce apoptosis. This discrepancy could not be explained by differences in bacterial uptake or total NADPH-oxidase activity. Suppressing phagocytosis by pretreating the neutrophils with cytochalasin b or by using nonopsonized bacteria did not prevent apoptosis. A supernatant from bacteria grown for 2 h in nutrient broth had a strong proapoptotic influence that was abrogated by heat treatment. Exposure to viableS. aureus or supernatant also led to activation of p38-mitogen-activated protein kinase in the neutrophils. Inhibition of this kinase with SB203580 reduced the apoptosis-inducing capacity of both bacteria and supernatant. We conclude that S. aureus activates p38-mitogen-activated protein kinase in neutrophils and induces apoptosis, probably mediated by a bacteria-derived soluble factor(s)
C1qRp, a myeloid cell receptor in blood, is predominantly expressed on endothelial cells in human tissue
Authors: Fonseca Maria I , Carpenter Philip M , Park Minha , Palmarini Gail , Nelson Edward L , Tenner Andrea J 
Published: September 2022

AbstractC1qRp is a type I cell surface glycoprotein that has been shown to enhance ingestion of suboptimally opsonized targets by phagocytes in vitro. In this study, we developed and characterized polyclonal antibodies to study the tissue distribution of this receptor targeted to either the N- or C-terminal portion of the molecule. C1qRp was detected in vascular endothelial cells and in a subset of pyramidal neurons in the brain, as well as neutrophils, but it was absent in most tissue macrophages. Analysis of in vitro differentiation of blood monocytes to dendritic cells demonstrated a down-regulation of the receptor as monocytes differentiate to dendritic cells, providing a possible explanation for the lack of reactivity of these cells in tissue. The predominant presence of C1qRp in endothelial cells, while compatible with a phagocytic role in host defense and/or clearance of cellular material, suggests other possible novel roles for this receptor.
Interplay between telomere length and telomerase in human leukocyte differentiation and aging
Authors: Weng Nan-ping 
Published: September 2022

AbstractBlood leukocytes derive from bone marrow hematopoietic stem cells anddifferentiate into multiple types of mature cells that includegranulocytes, monocytes, mast cells of myeloid lineage, and T and Blymphocytes of lymphoid lineage. Their distinctive paths ofdifferentiation and unique roles in immune response provide a model forcomparative analysis of biological parameters, such as telomere lengthand telomerase activity, in different types of leukocytes. Age has alsobeen associated with the decline in immune functions and with theattrition of telomere length in leukocytes. This review will summarizerecent progress in the study of telomere length and telomeraseexpression in leukocytes during differentiation and aging. In addition,I will attempt to shed new light on the roles of telomere andtelomerase in leukocyte function and potential clinicalinterventions.