Abstract:
:Neutrophils are indispensable in the innate immune defense against invading microorganisms. Neutrophils contain SVs and several subsets of granules that are essential for their function. Proteins present in neutrophil SVs and granules are synthesized during terminal granulopoiesis in the bone marrow. The heterogeneity of granules, as determined by marker proteins characteristic of each granule subset, is thought to result from differences in the biosynthetic windows of major classes of granule proteins, a process referred to as targeting by timing. Qualitative proteomic analysis of neutrophil granules, SVs, and plasma membrane has been performed before. Here, we performed subcellular fractionation on freshly isolated human neutrophils by nitrogen cavitation and density centrifugation on a four-layer Percoll gradient. Granule subsets were pooled and subjected to SDS-PAGE, and gel pieces were in-gel-digested with trypsin. The resulting peptides were analyzed using LTQ Orbitrap XL tandem MS. A total of 1292 unique proteins were identified and grouped, according to the neutrophil fraction, in which they displayed maximal expression. In addition to various known neutrophil proteins, several uncharacterized proteins were found, as well as proteins not described previously in neutrophils. To study the correlation between mRNA expression in neutrophil precursors and the localization of their cognate proteins, the distribution of 126 identified proteins was compared with their mRNA expression profiles. The neutrophil subcellular proteome profiles presented here may be used as a database in combination with the mRNA array database to predict and test the presence and localization of proteins in neutrophil granules and membranes.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Rørvig S,Østergaard O,Heegaard NH,Borregaard Ndoi
10.1189/jlb.1212619subject
Has Abstractpub_date
2013-10-01 00:00:00pages
711-21issue
4eissn
0741-5400issn
1938-3673pii
jlb.1212619journal_volume
94pub_type
杂志文章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::TLR agonists such as LPS and poly(I:C) induce expression of type I IFNs, such as IFN-α and -β, by macrophages. To examine the role of IFN-β in the induction of ISGs by LPS, we compared the ability of LPS to induce ISGF3 activity and ISG expression in bone marrow-derived macrophages from WT and Ifnb1(-/-) mice. We foun...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.2A0414-191R
更新日期:2014-10-01 00:00:00
abstract::Recognition of Gram-positive bacteria by Toll-like receptor 2 (TLR2) induces activation of proinflammatory pathways. In mice, sensitization with the Gram-positive Propionibacterium acnes followed by a challenge with the TLR4 ligand, lipopolysaccharide (LPS), results in fulminant hepatic failure. Here, we investigated ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0804448
更新日期:2005-12-01 00:00:00
abstract::Although IFN-alpha forms the foundation of therapy for chronic hepatitis C, only a minority of patients has a sustained response to IFN-alpha alone. The antiviral activities of IFN-alpha formed the rationale for its use in viral hepatitis. However, IFN-alpha and the other Type I IFNs are also pleiotropic immune regula...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,多中心研究
doi:10.1189/jlb.1006622
更新日期:2007-03-01 00:00:00
abstract::During inflammation the balance between cell activation and cell death is determined by the tight regulation of multiple intracellular enzyme cascades. Key regulatory steps often involve protein kinases. We show that the prototypical pro-inflammatory molecule, bacterial lipopolysaccharide, activates multiple protein k...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract::The seven transmembrane G protein-coupled receptor EBV-induced gene 2 (EBI2), also known as GPR183, is expressed in particular in immune cells. Activated by its endogenous ligands, which are a group of oxysterols, it functions as a chemo-attractant receptor, mediating cell migration. In coordination with other recepto...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/JLB.2VMR1217-510R
更新日期:2018-08-01 00:00:00
abstract::Successful remodeling of the uterine spiral arteries is essential for a complication-free pregnancy and is best described in terms of its morphologic features. The molecular mediators and cellular sources of spiral artery remodeling are not known, although a role for uterine leukocytes has been proposed. Immunohistoch...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1A0815-351R
更新日期:2016-08-01 00:00:00
abstract::The oxidative metabolic burst of stimulated human polymorphonuclear leukocytes (PMNs) has been evaluated by the measurement of oxygen consumption, chemiluminescence, and oxygen radicals (O2-, H2O2, OH-) derived from activation of the hexose monophosphate shunt (HMPS). PMNs from patients with chronic granulomatous dise...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.43.4.317
更新日期:1988-04-01 00:00:00
abstract::Macrophages activated for tumor cell killing by bacterial lipopolysaccharide (LPS) were shown to lose their cytolytic activity if exposed to physiological levels of prostaglandin E2 (PGE2). Increasing the LPS stimulus more than 100-fold over the amount needed to activate the cells did not substantially increase their ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.35.3.291
更新日期:1984-03-01 00:00:00
abstract::The persistent infection caused by hepatitis C virus (HCV) is presumably explained by a deficient immune response to the infection, but the basis for the inefficiency of immune-mediated virus eradication is not known in detail. This study addresses mechanisms of relevance to dysfunction of cytotoxic lymphocytes in HCV...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0704387
更新日期:2004-12-01 00:00:00
abstract::Precursors of dendritic cells (pre-DCs) arise in the bone marrow (BM), egress to the blood, and finally migrate to peripheral tissue, where they differentiate to conventional dendritic cells (cDCs). Upon their activation, antigen-bearing cDCs migrate from peripheral tissue to regional lymph nodes (LNs) in a manner dep...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1A0616-285R
更新日期:2017-05-01 00:00:00
abstract::Activation of Kupffer cells is a prominent feature of necro-inflammatory liver injury. We have recently demonstrated that 5-lipoxygenase (5-LO) and its accessory protein, 5-LO-activating protein (FLAP), are essential for the survival of Kupffer cells in culture, as their inhibition drives these liver resident macropha...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1204747
更新日期:2005-10-01 00:00:00
abstract::Mast cells are immune sentinels and a driving force in both normal and pathological contexts of inflammation, with a prominent role in allergic hypersensitivities. Crosslinking of FcεRI by allergen-bound IgE Abs leads to mast cell degranulation, resulting in an early-phase response and release of newly synthesized pro...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.3A0320-434R
更新日期:2020-05-01 00:00:00
abstract::Mast cell activation requires Cl(-) flux, which maintains the driving force for entry of extracellular calcium and initiates release of mediators such as histamine. However, chloride channel expression in mast cells has been poorly understood. For the first time, reverse transcriptase-polymerase chain reaction shows t...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate during pathologic conditions, such as cancer. Patients diagnosed with advanced metastatic cancers have an average survival of 12-24 mo, a survival time that hasn't changed significantly in the past 30 yr. ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.5VMR1116-458RRR
更新日期:2017-09-01 00:00:00
abstract::We recently demonstrated that the arachidonate metabolite 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) is converted by a highly specific dehydrogenase in human neutrophils to 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), which is a potent stimulator of these cells. The objective of this study was to dete...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.59.6.847
更新日期:1996-06-01 00:00:00
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 requ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.44.6.559
更新日期:1988-12-01 00:00:00
abstract::In mammals, macrophages are multifunctional cells. Apart from their scavenger role in the clearance of non-self materials such as microorganisms and altered-self materials such as apoptotic cells, senescent erythrocytes, immune complexes, and inflammatory products, they play a crucial role in the regulation of both in...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.62.6.702
更新日期:1997-12-01 00:00:00
abstract::Cytohesin-1 and ARNO are guanine nucleotide-exchange factors (GEFs) for ADP-ribosylation factor (Arf). Here, we show that ARNO is expressed in HL-60 cells and established that granulocytic differentiation induced with Me2SO stimulated cytohesin-1 but not ARNO expression. Cytohesin-1 levels in HL-60 granulocytes were s...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00
abstract::Spatial analyses of the distribution of Ca2+ in resting and activated T and B lymphocytes have shown that the bulk of increased [Ca2+]i appears to be associated with the nuclear region. These observations suggest that Ca2+ is released from the perinuclear space or that it diffuses to the nucleoplasm, or both. We have ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.62.6.874
更新日期:1997-12-01 00:00:00
abstract::In the absence of IL-10, colonic inflammation ensues, which is characterized by high levels of IL-17. Here, we demonstrate a direct correlation between ICOS expression and IL-17 production in cIELs. IL-10(-/-) mice had increased numbers of cIELs and greater colon weight. Although the CD69 early activation antigen was ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0409238
更新日期:2010-02-01 00:00:00
abstract::Elderly humans are more susceptible to bacterial infections because of declining immune status. We have investigated the effect of aging on neutrophil bactericidal responses, comparing neutrophil function in healthy, young (23-35 years) and elderly (>65 years) volunteers. Superoxide generation in response to fMLP was ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2001-12-01 00:00:00
abstract::We have investigated the role of the purinergic P2X7 receptor in the formation of multinucleated giant cells in human monocyte/macrophage cultures stimulated with either concanavalin A or phytohemagglutinin. Macrophage fusion can be blocked by a P2X7-selective pharmacological antagonist or by a mAb directed against th...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.66.5.723
更新日期:1999-11-01 00:00:00
abstract::Resting microglia comprise up to 13% of the cells in human central nervous system (CNS) white matter. Their large number and dendritic morphology make them ideally suited to survey the CNS for noxious stimuli. Upon activation microglia gradually lose dendritic processes and transform into typical phagocytic macrophage...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.56.6.732
更新日期:1994-12-01 00:00:00
abstract::The effects of brefeldin A, monensin, and the weak base NH4Cl on the biosynthesis and processing of cathepsin G and neutrophil elastase of myeloid cells were investigated. Monoblast-like U-937 cells were biosynthetically labeled with [35S]methionine, followed by subcellular fractionation, immunoprecipitation, and anal...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.55.1.50
更新日期:1994-01-01 00:00:00
abstract::Previous studies about basophils and mast cells identified the ability of IgE to up-regulate FcepsilonRI expression by a process that depends on stabilization of the surface receptor by IgE. However, the mechanism of loss from the cell surface, when unoccupied, is not known. The current studies have examined whether u...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0207103
更新日期:2007-10-01 00:00:00
abstract::MΦs are important sensory cells of the innate immune system and regulate immune responses through releasing different combinations of cytokines. In this study, we examined whether cytokines released by MΦs in response to the probiotic bacterial strain GR-1 modulate the responses of DCs. The cytokine profile released b...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0810445
更新日期:2011-06-01 00:00:00
abstract::The ability of encapsulated and acapsular strains of Cryptococcus neoformans to activate dendritic cells (DC) derived from monocytes stimulated with granulocyte macrophage-colony stimulating factor and interleukin-4 was evaluated. Profound differences in DC response to encapsulated and acapsular C. neoformans strains ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1002476
更新日期:2003-09-01 00:00:00
abstract::The promoters of the IL-8, MCP-1, and RANTES genes contain binding sites for the redox-responsive transcription factors AP-1 and NF-kappaB, which have been shown to be important for their expression. In this overview, we present evidence from our laboratories that the stimulus-specific regulation of these chemokines b...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.65.3.291
更新日期:1999-03-01 00:00:00
abstract::IL-31, a newly identified member of the IL-6 cytokine family, is involved in many pathological conditions, including atopic dermatitis and pruritis. In this study, we investigated how expression of IL-31 is regulated in T cells and mast cells. We observed that expression of IL-31 required a calcium signal and was depe...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0111020
更新日期:2012-02-01 00:00:00