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Journal of Leukocyte Biology

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https://www.readbyqxmd.com/read/28223316/energy-metabolism-drives-myeloid-derived-suppressor-cell-differentiation-and-functions-in-pathology
#1
REVIEW
Antonio Sica, Laura Strauss
Over the last decade, a heterogeneous population of immature myeloid cells with major regulatory functions has been described in cancer and other pathologic conditions and ultimately defined as MDSCs. Most of the early work on the origins and functions of MDSCs has been in murine and human tumor bearers in which MDSCs are known to be immunosuppressive and to result in both reduced immune surveillance and antitumor cytotoxicity. More recent studies, however, suggest that expansion of these immature myeloid cells may be linked to most, if not all, chronic and acute inflammatory processes...
February 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28196851/inhibition-of-lipopolysaccharide-induced-osteoclast-formation-and-bone-resorption-in-vitro-and-in-vivo-by-cysteine-proteinase-inhibitors
#2
Fredrik Strålberg, Ali Kassem, Franciszek Kasprzykowski, Magnus Abrahamson, Anders Grubb, Catharina Lindholm, Ulf H Lerner
Inflammation-induced bone destruction is a major treatment target in many inflammatory skeletal diseases. The aim of this study was to investigate if the cysteine proteinase inhibitors cystatin C, fungal cysteine proteinase inhibitor (E-64), and N-benzyloxycarbonyl-arginyl-leucyl-valyl-glycyl-diazomethane acetate (Z-RLVG-CHN2) can inhibit LPS-induced osteoclast formation. Mouse bone marrow macrophages (BMMs) were isolated and primed with receptor activator of NF-κB ligand (RANKL) for 24 h, followed by stimulation with LPS, with and without inhibitors...
February 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28196850/endothelial-cell-activation-in-central-nervous-system-inflammation
#3
REVIEW
Fengjiao Wu, Lixin Liu, Hong Zhou
Leukocyte migration across the endothelial barrier plays an essential role in CNS inflammation. The migration process requires complex endothelial adhesion molecules concentrated at the junctions of endothelial cells. Recent findings suggest that cerebral endothelial cells play an active role in the pathogenesis of CNS inflammatory diseases. This review describes our current understanding of the effects of various inflammatory mediators of leukocyte migration on cerebral endothelial cells, the mechanisms underlying the leukocyte-endothelial cell interactions, and the crosstalk between endothelial cells and glial cells or platelets...
February 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28193736/down-regulation-of-cd73-on-b-cells-of-patients-with-viremic-hiv-correlates-with-b-cell-activation-and-disease-progression
#4
Eun-Seong Kim, Christin Ackermann, Ilona Tóth, Patrick Dierks, Johanna M Eberhard, Raluca Wroblewski, Felix Scherg, Matthias Geyer, Reinhold E Schmidt, Claudia Beisel, Maximilian Bockhorn, Friedrich Haag, Jan van Lunzen, Julian Schulze Zur Wiesch
Recently, alterations of the T cell expression of the ectonucleotidases, CD39 and CD73, during HIV infection have been described. Here, peripheral (n = 70) and lymph nodal B cells (n = 10) of patients with HIV at different stages of disease as well as uninfected individuals were analyzed via multicolor flow cytometry with regard to expression of CD39 and CD73 and differentiation, proliferation, and exhaustion status. Patients with chronic, untreated HIV showed a significantly decreased frequency of CD73-expressing B cells (P < 0...
February 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28179539/smoking-reduces-circulating-cd26-hi-cd161-hi-mait-cells-in-healthy-individuals-and-patients-with-multiple-sclerosis
#5
Cecilie Ammitzbøll, Lars Börnsen, Jeppe Romme Christensen, Rikke Ratzer, Birgitte Romme Nielsen, Helle B Søndergaard, Marina R von Essen, Finn Sellebjerg
Upon chronic cigarette smoke exposure, inhaled antigens and irritants cause altered lung immune homeostasis. Circulating immune cells are affected, and smoking is associated with an increased risk of developing various disorders, including multiple sclerosis (MS). This study was conducted to determine the impact of smoking on circulating immune cell subsets. Furthermore, we determined whether any smoking-associated changes were related to MS. With the use of flow cytometry, CFSE assays, and ELISpot assays, we analyzed circulating immune cell phenotypes and quantified antigen-induced proliferation and cytokine secretion in smokers and nonsmokers in a cohort of 100 healthy individuals (HI)...
February 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28179538/the-clinical-evidence-for-targeting-human-myeloid-derived-suppressor-cells-in-cancer-patients
#6
REVIEW
Richard P Tobin, Dana Davis, Kimberly R Jordan, Martin D McCarter
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that represent a formidable obstacle to the successful treatment of cancer. Patients with high frequencies of MDSCs have significantly decreased progression-free survival (PFS) and overall survival (OS). Whereas there is experimental evidence that the reduction of the number and/or suppressive function of MDSCs in mice improves the efficacy of anti-cancer therapies, there is notably less evidence for this therapeutic strategy in human clinical trials...
February 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28179537/early-tyrosine-phosphorylation-events-following-adenosine-a2a-receptor-in-human-neutrophils-identification-of-regulated-pathways
#7
Miriam S Giambelluca, Marc Pouliot
Activation of the adenosine 2A receptor (A2AR) elevates intracellular levels of cAMP and acts as a physiologic inhibitor of inflammatory neutrophil functions. In this study, we looked into the impact of A2AR engagement on early phosphorylation events. Neutrophils were stimulated with well-characterized proinflammatory agonists in the absence or presence of an A2AR agonist {3-[4-[2-[ [6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]purin-2-yl]amino] ethyl] phenyl] propanoic acid (CGS 21680)}, PGE2, or a mixture of the compounds RO 20-1724 and forskolin...
February 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28148720/distinct-functions-of-cxcr4-ccr2-and-cx3cr1-direct-dendritic-cell-precursors-from-the-bone-marrow-to-the-lung
#8
Hideki Nakano, Miranda R Lyons-Cohen, Gregory S Whitehead, Keiko Nakano, Donald N Cook
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 dependent on the chemokine receptor, CCR7. To maintain immune homeostasis, these departing cDCs must be replenished by new cDCs that develop from pre-DCs, but the molecular signals that direct pre-DC trafficking from the BM to the blood and peripheral tissues remain poorly understood...
February 1, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28148719/matricellular-proteins-tune-myeloid-derived-suppressor-cell-recruitment-and-function-in-breast-cancer
#9
REVIEW
Claudia Chiodoni, Sabina Sangaletti, Mario P Colombo
Solid tumor progression is often associated with the expansion of myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature myeloid cells that actively foster tumor growth and metastatic dissemination through a plethora of mechanisms, including, but not limited to, their major suppressive activity on the immune response. Indeed, MDSCs may sustain tumor progression by dynamically remodeling the tumor microenvironment through the production of angiogenic factors and metalloproteases, by helping the establishment of a premetastatic niche, and by promoting stemness and epithelial-to-mesenchymal transition (EMT) features in tumor cells...
February 1, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28148718/role-of-myeloid-derived-suppressor-cells-in-allogeneic-hematopoietic-cell-transplantation
#10
REVIEW
Brent H Koehn, Bruce R Blazar
Graft-versus-host disease (GVHD) can be a devastating complication for as many as a third of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). A role for myeloid cells in the amplification of GVHD has been demonstrated; however, less is understood about a potential regulatory role that myeloid cells play or whether such cells may be manipulated and applied therapeutically. Myeloid-derived suppressor cells (MDSCs) are a naturally occurring immune regulatory population that are engaged and expand shortly after many forms of immune distress, including cancer, trauma, and infection...
February 1, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28122813/hs1-deficiency-impairs-neutrophil-recruitment-in-vivo-and-activation-of-the-small-gtpases-rac1-and-rap1
#11
Joanna Latasiewicz, Annette Artz, Ding Jing, Mariana Pacheco Blanco, Silke M Currie, Martha Velázquez Avila, Michael Schnoor, Dietmar Vestweber
Neutrophil extravasation is a critical step of the innate immune system's response to inflammation. This multistep process is tightly regulated by adhesion and signaling molecules in the endothelium and neutrophils. Activation of the β2 integrin LFA-1 is critical for adhesion of leukocytes to postcapillary venules. This step requires coordinated activation of signaling pathways in chemokine-stimulated neutrophils, including GTPase activation and cytoskeletal remodeling, leading to conformational changes in LFA-1...
January 25, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28115476/long-term-consequences-of-topical-dexamethasone-treatment-during-acute-corneal-hsv-1-infection-on-the-immune-system
#12
Ana J Chucair-Elliott, Meghan M Carr, Daniel J J Carr
Herpes simplex virus type 1 (HSV-1) is a leading cause of neurotrophic keratitis (NTK). NTK is characterized by decreased corneal sensation from damage to the corneal sensory fibers. We have reported on the regression of corneal nerves and their function during acute HSV-1 infection. That nerve loss is followed by an aberrant process of nerve regeneration during the latent phase of infection that lacks functional recovery. We recently showed the elicited immune response in the infected cornea, and not viral replication itself, is part of the mechanism responsible for the nerve degeneration process after infection...
January 23, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28096301/phosphoinositol-3-phosphate-acts-as-a-timer-for-reactive-oxygen-species-production-in-the-phagosome
#13
Zhi Min Song, Leïla Bouchab, Elodie Hudik, Romain Le Bars, Oliver Nüsse, Sophie Dupré-Crochet
Production of reactive oxygen species (ROS) in the phagosome by the NADPH oxidase is critical for mammalian immune defense against microbial infections and phosphoinositides are important regulators in this process. Phosphoinositol 3-phosphate (PI(3)P) regulates ROS production at the phagosome via p40(phox) by an unknown mechanism. This study tested the hypothesis that PI(3)P controls ROS production by regulating the presence of p40(phox) and p67(phox) at the phagosomal membrane. Pharmacologic inhibition of PI(3)P synthesis at the phagosome decreased the ROS production both in differentiated PLB-985 cells and human neutrophils...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28096300/enhanced-suppression-of-polyclonal-cd8-25-regulatory-t-cells-via-exosomal-arming-of-antigen-specific-peptide-mhc-complexes
#14
Chuanyong Mu, Xueshu Zhang, Lu Wang, Aizhang Xu, Khawaja Ashfaque Ahmed, Xueqin Pang, Rajni Chibbar, Andrew Freywald, Jianan Huang, Yehan Zhu, Jim Xiang
Compared with CD4(+)25(+) regulatory T cells (Tregs), the mechanisms for natural, polyclonal CD8(+)25(+) Treg immune suppression have been significantly less studied. We previously showed that polyclonal T cells can acquire antigen-specific targeting activity through arming with exosomal peptide-MHC (pMHC). In this study, we assessed the suppressive effect of CD8(+)25(+) Tregs or CD8(+)25(+) Tregs armed with ovalbumin (OVA)-specific exosomes on other immune cells and OVA-specific dendritic cell (DCOVA)-stimulated antitumor immunity...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28096299/exosomes-from-eosinophils-autoregulate-and-promote-eosinophil-functions
#15
José Antonio Cañas, Beatriz Sastre, Carla Mazzeo, Mar Fernández-Nieto, José Manuel Rodrigo-Muñoz, Andrés González-Guerra, Manuel Izquierdo, Pilar Barranco, Santiago Quirce, Joaquín Sastre, Victoria Del Pozo
Eosinophils are able to secrete exosomes that have an undefined role in asthma pathogenesis. We hypothesized that exosomes released by eosinophils autoregulate and promote eosinophil function. Eosinophils of patients with asthma (n = 58) and healthy volunteers (n = 16) were purified from peripheral blood, and exosomes were isolated and quantified from eosinophils of the asthmatic and healthy populations. Apoptosis, adhesion, adhesion molecules expression, and migration assays were performed with eosinophils in the presence or absence of exosomes from healthy and asthmatic individuals...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28096298/mfg-e8-derived-peptide-attenuates-adhesion-and-migration-of-immune-cells-to-endothelial-cells
#16
Yohei Hirano, Weng-Lang Yang, Monowar Aziz, Fangming Zhang, Barbara Sherry, Ping Wang
Milk fat globule-epidermal growth factor-factor 8 (MFG-E8) plays an immunomodulatory role in inflammatory diseases. MFG-E8-derived short peptide (MSP68) greatly reduces neutrophil infiltration and injury in the lung during sepsis. In this study, we examined the effect of MSP68 on chemotaxis of various immune cells and its regulatory mechanism. Bone marrow-derived neutrophils (BMDNs) from C57BL/6 mice, human monocyte THP-1 cell line, and human T lymphocyte Jurkat cell line were used for adhesion and migration assays using a Transwell method in the presence of MSP68...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28096297/frontline-science-tumor-necrosis-factor-%C3%AE-stimulation-and-priming-of-human-neutrophil-granule-exocytosis
#17
Kenneth R McLeish, Michael L Merchant, T Michael Creed, Shweta Tandon, Michelle T Barati, Silvia M Uriarte, Richard A Ward
Neutrophil granule exocytosis plays an important role in innate and adaptive immune responses. The present study examined TNF-α stimulation or priming of exocytosis of the 4 neutrophil granule subsets. TNF-α stimulated exocytosis of secretory vesicles and gelatinase granules and primed specific and azurophilic granule exocytosis to fMLF stimulation. Both stimulation and priming of exocytosis by TNF-α were dependent on p38 MAPK activity. Bioinformatic analysis of 1115 neutrophil proteins identified by mass spectrometry as being phosphorylated by TNF-α exposure found that actin cytoskeleton regulation was a major biologic function...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28087652/differential-regulation-of-cd103-%C3%AE-e-integrin-expression-in-human-dendritic-cells-by-retinoic-acid-and-toll-like-receptor-ligands
#18
Mandi M Roe, Steve Swain, T Andrew Sebrell, Marisa A Sewell, Madison M Collins, Brian A Perrino, Phillip D Smith, Lesley E Smythies, Diane Bimczok
CD103 (αE integrin) is an important dendritic cell (DC) marker that characterizes functionally distinct DC subsets in mice and humans. However, the mechanism by which CD103 expression is regulated in human DCs and the role of CD103 for DC function are not very well understood. Here, we show that retinoic acid (RA) treatment of human monocyte-derived DCs (MoDCs) increased the ability of the DCs to synthesize RA and induced MoDC expression of CD103 and β7 at the mRNA and protein level. In contrast, RA was unable to induce the expression of CD103 in primary human DCs isolated from the gastric mucosa...
January 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28087651/frontline-science-multiple-cathepsins-promote-inflammasome-independent-particle-induced-cell-death-during-nlrp3-dependent-il-1%C3%AE-activation
#19
Gregory M Orlowski, Shruti Sharma, Jeff D Colbert, Matthew Bogyo, Stephanie A Robertson, Hiroshi Kataoka, Francis K Chan, Kenneth L Rock
Sterile particles cause several chronic, inflammatory diseases, characterized by repeating cycles of particle phagocytosis and inflammatory cell death. Recent studies have proposed that these processes are driven by the NLRP3 inflammasome, a platform activated by phagocytosed particles, which controls both caspase-1-dependent cell death (pyroptosis) and mature IL-1β secretion. After phagocytosis, particles can disrupt lysosomes, and inhibitor studies have suggested that the resulting release of a lysosomal protease-cathepsin B-into the cytosol somehow activates NLRP3...
January 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28062573/deficiency-of-n-myristoylation-reveals-calcineurin-activity-as-regulator-of-ifn-%C3%AE-producing-%C3%AE-%C3%AE-t-cells
#20
Francesca Rampoldi, Fabian Brunk, Mahnaz Bonrouhi, Giuseppina Federico, Damir Krunic, Stefan Porubsky, Hermann-Josef Gröne, Zoran V Popovic
γδ T cell subsets can be characterized, in part, by their secretion of select proinflammatory cytokines. The molecular mechanisms driving the diverse fates of γδ T cells have not been elucidated. We have previously shown that the attachment of myristic acid to the N-terminal glycine of proteins, termed N-myristoylation, is essential for αβ T cell development and activation. Here, we explore the potential role of this lipid modification on the activation of γδ T cells. In the absence of N-myristoylation, the CD27(+) γδ T cell subset was dominantly affected...
January 6, 2017: Journal of Leukocyte Biology
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