Abstract:
:Neutrophil's responses to G protein-coupled chemoattractants are highly dependent on store-operated calcium (Ca(2+)) entry (SOCE). Platelet-activating factor (PAF), a primary chemoattractant, simultaneously increases cytosolic-free Ca(2+), intracellular pH (pH(i)), ERK1/2, and Akt/protein kinase B (PKB) phosphorylation. In this study, we looked at the efficacy of several putative SOCE inhibitors and whether SOCE mediates intracellular alkalinization, ERK1/2, and Akt/PKB phosphorylation in bovine neutrophils. We demonstrated that the absence of external Ca(2+) and the presence of EGTA reduced the intracellular alkalinization and ERK1/2 phosphorylation induced by PAF, apparently via SOCE influx inhibition. Next, we tested the efficacy of several putative SOCE inhibitors such as 2-aminoethoxydiphenyl borate (2-APB), capsaicin, flufenamic acid, 1-{beta-[3-(4-methoxy-phenyl)propoxy]-4-methoxyphenethyl}-1H-imidazole hydrochloride (SK&F 96365), and N-(4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide (BTP2) on Ca(2+) entry induced by PAF or thapsigargin. 2-APB was the most potent SOCE inhibitor, followed by capsaicin and flufenamic acid. Conversely, SK&F 96365 reduced an intracellular calcium ([Ca(2+)](i)) peak but SOCE partially. BTP2 did not show an inhibitory effect on [Ca(2+)](i) following PAF stimuli. 2-APB strongly reduced the pH(i) recovery, whereas the effect of flufenamic acid and SK&F 96365 was partial. Capsaicin and BTP2 did not affect the pH(i) changes induced by PAF. Finally, we observed that 2-APB reduced the ERK1/2 and Akt phosphorylation completely, whereas the inhibition with flufenamic acid was partial. The results suggest that 2-APB is the most potent SOCE inhibitor and support a key role of SOCE in pH alkalinization and PI-3K-ERK1/2 pathway control. Finally, 2-APB could be an important tool to characterize Ca(2+) signaling in neutrophils.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Sandoval AJ,Riquelme JP,Carretta MD,Hancke JL,Hidalgo MA,Burgos RAdoi
10.1189/jlb.0307196subject
Has Abstractpub_date
2007-11-01 00:00:00pages
1266-77issue
5eissn
0741-5400issn
1938-3673pii
jlb.0307196journal_volume
82pub_type
杂志文章abstract::The viral CC chemokines MC148, encoded by the poxvirus molluscum contagiosum, and viral macrophage inflammatory protein (vMIP)-I and vMIP-II, encoded by human herpesvirus 8, were probed on the murine CC receptor (CCR) 8 in parallel with human CCR8. In calcium mobilization assays, vMIP-I acted as a high-affinity agonis...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2001-08-01 00:00:00
abstract::Evidence that gamma/delta T cells play a broad, immunoregulatory role has been accumulating steadily. We show here that myeloid cells are disregulated after peritoneal infection with Listeria monocytogenes in mice lacking gamma/delta T cells. Inflammatory populations of neutrophils and monocytes recruited to the site ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1103574
更新日期:2004-07-01 00:00:00
abstract::During the neoplastic progression, macrophages as well as dendritic and NK cells are attracted into the tumor site and initiate the immune response against transformed cells. They activate and present tumor antigens to T cells, which are then activated to kill tumor cells. However, tumor cells are often capable of esc...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.1105656
更新日期:2006-10-01 00:00:00
abstract::Proteoglycans (PGs) play a dominant role within the bone marrow (BM), but their role in homing of transplanted hematopoietic progenitor cells (HPC) is unknown. In this study, the role of heparan sulfate (HS) PGs on BM endothelium as adhesive structures was investigated. HPC (primary CD34+ cells and cell line KG-1a) we...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1202593
更新日期:2003-12-01 00:00:00
abstract::Glucocorticoids, such as dexamethasone (Dex), are used clinically in the treatment of various inflammatory diseases. Dex acts by inhibiting the expression of inflammatory mediators, such as tumor necrosis factor alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1). It is surprising that Dex enhances bacter...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0204068
更新日期:2004-07-01 00:00:00
abstract::Dendritic cells (DCs) are specialized APCs present in all tissues, including tumors. They play a major role in orchestrating immune responses and were shown to occur in various functional states in tumors. In this respect, immunogenic tumor-associated DCs (TADCs) are required to initiate and sustain T cell-dependent a...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.4MR1116-466R
更新日期:2017-08-01 00:00:00
abstract::The last 18 months have witnessed the characterization of several new members of the tumor necrosis factor (TNF) receptor family. Among these are five receptors for the cytotoxic ligand TRAIL (TNF-related apoptosis-inducing ligand). Two of these receptors, TRAIL-R1 and TRAIL-R2, contain classical cytoplasmic death dom...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.65.5.535
更新日期:1999-05-01 00:00:00
abstract::IL-27, an IL-12 family member, was initially described as a proinflammatory cytokine. Nevertheless, it also poses anti-inflammatory activity, being involved in suppressing development of TH-17 cells as well as in the induction of inhibitory Tr1 cells. Recent data obtained in mice suggest that it can down-modulate the ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1209788
更新日期:2011-06-01 00:00:00
abstract::The lineage-specific Charcot-Leyden crystal (CLC) protein is found in human eosinophils and basophils where it comprises 7-10% of the cellular protein content. Previous work from our laboratory has identified the motif GGAGA[A/G] as a powerful enhancer of gene transcription ill two eosinophil ribonuclease genes. To ev...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.67.5.691
更新日期:2000-05-01 00:00:00
abstract::The primary targets of HIV are CD4(+) T cells and macrophages. HIV infection is associated with an increase in apoptosis of infected and uninfected CD4(+) T cells, and these infected cells undergo apoptosis and produce HIV virions with phosphatidylserine (PS) on their surface. During phagocytosis of apoptotic cells, m...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1105638
更新日期:2006-10-01 00:00:00
abstract::Intracellular zinc homeostasis is strictly regulated by zinc binding proteins and zinc transporters. In the present study, we quantified in a first global view the expression of all characterized human zinc exporters (hZnT-1-9) in different leukocyte subsets in response to zinc supplementation and depletion and analyz...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0307148
更新日期:2008-02-01 00:00:00
abstract::The influence of ethanol (EtOH) on multiple dendritic cell (DC) subsets, in the steady state or following their mobilization in vivo, has not been characterized. Herein, generation of mouse bone marrow-derived DC (BMDC) in response to fms-like tyrosine kinase 3 ligand was inhibited by physiologically relevant concentr...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0905517
更新日期:2006-05-01 00:00:00
abstract::PGE(2) and other cAMP-elevating agents are known to down-regulate most functions stimulated by fMLP in human polymorphonuclear neutrophils. We reported previously that the inhibitory potential of PGE(2) resides in its capacity to suppress fMLP-stimulated PI-3Kgamma activation via the PGE(2) receptor EP(2) and hence, t...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0406256
更新日期:2007-06-01 00:00:00
abstract::The immune system of astronauts is disturbed during and after spaceflight. This situation may result from stressors encountered during the flight (microgravity, radiation, psychological stress, or confinement) or from physiological changes (demineralization or fluid shift). Therefore, ground-based investigations shoul...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.54.3.209
更新日期:1993-09-01 00:00:00
abstract::The receptor for urokinase plasminogen activator (uPAR; CD87) is a 50- to 65-kDa glycosylphosphatidylinositol (GPI)-anchored glycoprotein expressed by leukocytes and tumor cells where it facilitates uPA-dependent, plasmin-mediated pericellular proteolysis during cellular invasion. Because uPAR is inducibly shed into c...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.64.2.203
更新日期:1998-08-01 00:00:00
abstract::Activation of beta2 integrins is necessary for neutrophil adhesion and full activation of neutrophil effector functions. We demonstrated previously that inhibition of protein kinase A (PKA) activity in quiescent neutrophils is sufficient to increase beta2-integrin cell surface expression, affinity, and adhesion. Thus,...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0405192
更新日期:2008-04-01 00:00:00
abstract::Ketorolac tromethamine, a new nonsteroidal anti-inflammatory agent of the pyrrolo-pyrrole group, was assayed for inhibitory effects on polymorphonuclear leukocytes (PMN) in a variety of systems. Ketorolac inhibited PMN superoxide anion generation, lysozyme release, myeloperoxidase release, adherence to plastic surface...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.51.5.490
更新日期:1992-05-01 00:00:00
abstract::Macrophage activation by IFN-gamma results in a cascade of gene expression. To identify genes activated in mouse peritoneal macrophages by IFN-gamma, we created a cDNA subtraction library of IFN-gamma-induced genes. We have isolated from this subtraction library a novel cDNA clone, called Mg21, whose mRNA is absent in...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.57.3.477
更新日期:1995-03-01 00:00:00
abstract::GM-CSF is well recognized as a proliferative agent for hematopoietic cells and exerts a priming function on neutrophils. The aim of this study was to determine if GM-CSF has a role as a neutrophil chemoattractant in vivo and if it can contribute to recruitment during intestinal inflammation. Initial studies in vitro, ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0809546
更新日期:2011-06-01 00:00:00
abstract::Vitamin B9, commonly known as folate, is an essential cofactor for one-carbon metabolism that enters cells through three major specialized transporter molecules (RFC, FR, and PCFT), which differ in expression pattern, affinity for substrate, and ligand-binding pH dependency. We now report that the expression of the fo...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0613345
更新日期:2014-05-01 00:00:00
abstract::The colony-stimulating factors (CSF) belong to a group of proteins which regulate blood cell production. Human monocytes allowed to adhere express high levels of M-CSF transcripts and secreted protein at 24 h in the presence but not in the absence of indomethacin (Indo), an inhibitor of prostaglandin E (PGE) productio...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.47.3.275
更新日期:1990-03-01 00:00:00
abstract::CXC chemokines, which induce angiogenesis, have glutamine-leucine-arginine amino acid residues (ELR motif) in the amino terminus and bind CXCR2 and the Duffy antigen chemokine-binding protein. Duffy, a seven transmembrane protein that binds CXC and CC chemokines, has not been shown to couple to trimeric G proteins or ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::The RAGE binds multiple ligand families linked to hyperglycemia, aging, inflammation, neurodegeneration, and cancer. Activation of RAGE by its ligands stimulates diverse signaling cascades. The recent observation that the cytoplasmic domain of RAGE interacts with diaphanous or mDia-1 links RAGE signal transduction to ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.0409230
更新日期:2009-09-01 00:00:00
abstract::LPS has been widely used to induce inflammatory pain, attributing to production of inflammatory cytokines and sensitization of nociceptors. Paeoniflorin (PF) possesses anti-nociceptive property, but its effect on LPS-induced inflammatory pain has not been investigated. In this study, we aimed to investigate the analge...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.3MA0220-355R
更新日期:2020-07-01 00:00:00
abstract::Neutrophils phagocytize high-valency immune complexes (HIC) by an Fc gamma receptor-mediated mechanism, activating an oxidative burst and initiating degranulation. In contrast, neutrophils exhibit chemotaxis to N-formylated peptides [e.g., N-formyl-methionyl-leucyl-phenylalanine (fMLP)] and secrete far fewer oxidants ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.61.4.522
更新日期:1997-04-01 00:00:00
abstract::This report focuses on the modulatory role of endogenous H(2)O(2) on lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma)-induced inducible nitric oxide synthase (NOS2) gene expression in rat peritoneal macrophages. Exogenously added H(2)O(2) was initially found to inhibit the synthesis of NOS2, which prompted us to ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1003459
更新日期:2004-06-01 00:00:00
abstract::Most staphylococci produce short α-type PSMs and about twice as long β-type PSMs that are potent leukocyte attractants and toxins. PSMs are usually secreted with the N-terminal formyl group but are only weak agonists for the leukocyte FPR1. Instead, the FPR1-related FPR2 senses PSMs efficiently and is crucial for leuk...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.2A0514-275R
更新日期:2015-04-01 00:00:00
abstract::T cell Ig and mucin domain-containing molecule 3 (Tim-3) has been found to play important roles in autoimmune diseases, but whether Tim-3-mediated engulfment of apoptotic cells is involved in systemic lupus erythematosus (SLE) remains to be elucidated. In this study, we verified the role of human Tim-3 (hTim-3) as the...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.3HI0117-005RR
更新日期:2017-12-01 00:00:00
abstract::Several lines of evidence support the concept that NK cells play an important role in control of hepatitis C virus (HCV) infection via cytokine secretion and cytotoxicity. IL-7 is a homeostatic cytokine with a role in T cell development, activation, proliferation, and cytokine secretion. The IL-7Rα chain [cluster of d...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.5A1116-456R
更新日期:2017-07-01 00:00:00
abstract::Hematopoietic cell differentiation takes place in phenotypically recognizable stages characterized by morphology as well as by the expression of enzymes and surface markers. It is recognized that differentiation results from an interaction of environmental cues, such as cytokines and hormones, with internal cellular p...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.67.4.559
更新日期:2000-04-01 00:00:00