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Journal of Leukocyte Biology

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https://www.readbyqxmd.com/read/28811319/galectin-8-activates-dendritic-cells-and-stimulates-antigen-specific-immune-response-elicitation
#1
Julieta Carabelli, Valeria Quattrocchi, Alejandra D'Antuono, Patricia Zamorano, María Virginia Tribulatti, Oscar Campetella
Galectin-8 (Gal-8) is a mammalian β-galactoside-binding lectin, endowed with proinflammatory properties. Given its capacity to enhance antigen-specific immune responses in vivo, we investigated whether Gal-8 was also able to promote APC activation to sustain T cell activation after priming. Both endogenous [dendritic cells (DCs)] and bone marrow-derived DCs (BMDCs) treated with exogenous Gal-8 exhibited a mature phenotype characterized by increased MHC class II (MHCII), CD80, and CD86 surface expression. Moreover, Gal-8-treated BMDCs (Gal-8-BMDCs) stimulated antigen-specific T cells more efficiently than immature BMDCs (iBMDCs)...
August 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28807929/human-mucosal-associated-invariant-t-mait-cells-possess-capacity-for-b-cell-help
#2
Michael S Bennett, Shubhanshi Trivedi, Anita S Iyer, J Scott Hale, Daniel T Leung
Mucosal-associated invariant T (MAIT) cells are an innate-like T-cell subset, restricted by the nonclassic MHC class I-related protein MR1 and enriched at mucosal sites. Human studies have shown an association between MAIT cells and pathogen-specific antibody responses. In this study, we investigate the effect of human MAIT cells on B cells ex vivo. We found that supernatants from microbe- or cytokine-stimulated MAIT cells, when added to purified autologous B cells, increase frequencies of plasmablasts and promote IgA, IgG, and IgM production...
August 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28801344/frontline-science-macrophage-derived-exosomes-promote-neutrophil-necroptosis-following-hemorrhagic-shock
#3
Yang Jiao, Zhigang Li, Patricia A Loughran, Erica K Fan, Melanie J Scott, Yuehua Li, Timothy R Billiar, Mark A Wilson, Xueyin Shi, Jie Fan
Hemorrhagic shock (HS) renders patients susceptible to development of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) through mechanisms that are, as yet, unclear. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that controls cell release of inflammatory mediators from innate immune cells, such as polymorphonuclear neutrophils (PMNs), and critically regulates the progress of inflammation. In this study, we investigated the mechanisms of alveolar macrophage (AMϕ) effects on PMN necroptosis following HS...
August 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28798145/tnf-induces-neutrophil-adhesion-via-formin-dependent-cytoskeletal-reorganization-and-activation-of-%C3%AE-integrin-function
#4
Angélica Aparecida Antoniellis Silveira, Venina Marcela Dominical, Camila Bononi Almeida, Hanan Chweih, Wilson Alves Ferreira, Cristina Pontes Vicente, Fabio Trindade Maranhão Costa, Claudio C Werneck, Fernando Ferreira Costa, Nicola Conran
Although essential for inflammatory responses, leukocyte recruitment to blood vessel walls in response to inflammatory stimuli, such as TNF-α, can contribute to vascular occlusion in inflammatory diseases, including atherosclerosis. We aimed to further characterize the mechanisms by which TNF stimulates adhesive and morphologic alterations in neutrophils. Microfluidic and intravital assays confirmed the potent effect that TNF has on human and murine neutrophil adhesion and recruitment in vitro and in vivo, respectively...
August 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28798144/frontline-science-leishmania-mexicana-amastigotes-can-replicate-within-neutrophils
#5
Benjamin P Hurrell, Manon Beaumann, Sandrina Heyde, Ivo B Regli, Andreas J Müller, Fabienne Tacchini-Cottier
Cutaneous leishmaniasis is a neglected tropical disease, causing a spectrum of clinical manifestations varying from self-healing to unhealing lesions that may be very difficult to treat. Emerging evidence points to a detrimental role for neutrophils during the first hours following infection with many distinct Leishmania species (spp.) at a time when the parasite is in its nonreplicative promastigote form. Neutrophils have also been detected at later stages of infection in unhealing chronic cutaneous lesions...
August 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28768708/identification-of-compounds-that-decrease-numbers-of-mycobacteria-in-human-macrophages-in-the-presence-of-serum-amyloid-p
#6
Wang Xiang, Nehemiah Cox, Richard H Gomer
Mϕs are a heterogeneous population of cells and include classically activated Mϕs (M1) and alternatively activated Mϕs (M2). Mϕs can change from M1 to M2 and vice versa in response to environmental stimuli. Serum amyloid P (SAP) is a constitutive plasma protein that polarizes Mϕs to an M2 phenotype, and part of this effect is mediated through FcγRI receptors. In an effort to find ways to alter Mϕs phenotypes, we screened for compounds that can block the SAP-FcγRI interaction. From a screen of 3000 compounds, we found 12 compounds that reduced the ability of fluorescently labeled human SAP to bind cells expressing human FcγRI...
August 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28760822/reactivation-of-g%C3%AE-i-coupled-formyl-peptide-receptors-is-inhibited-by-g%C3%AE-q-selective-inhibitors-when-induced-by-signals-generated-by-the-platelet-activating-factor-receptor
#7
André Holdfeldt, Agnes Dahlstrand Rudin, Michael Gabl, Zahra Rajabkhani, Gabriele M König, Evi Kostenis, Claes Dahlgren, Huamei Forsman
Formyl peptide receptor (FPR)-desensitized neutrophils display increased production/release of superoxide (O2(-)) when activated by platelet-activating factor (PAF), a priming of the response achieved through a unique receptor crosstalk mechanism. The aim of this study was to determine the effect of an inhibitor selective for small, heterotrimeric G proteins belonging to the Gαq subclass on that receptor crosstalk. We show that signals generated by FPRs and the PAF receptor (PAFR) induce activation of the neutrophil O2(-), producing NADPH-oxidase, and that response was sensitive to Gαq inhibition in cells activated by PAF, but no inhibition was obtained in cells activated by FPR agonists...
July 31, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28754800/frontline-science-tim-3-mediated-dysfunctional-engulfment-of-apoptotic-cells-in-sle
#8
Di Zhao, Min Guo, Bing Liu, Qinghai Lin, Tingting Xie, Qianqian Zhang, Xiaoxia Jia, Qiang Shu, Xiaohong Liang, Lifen Gao, Chunhong Ma
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 receptor of phosphatidylserine (PS) in human embryonic kidney (HEK)293 cells, which initiated the engulfment of apoptotic cells. Both IgV and the mucin domain of Tim-3 were crucial in the phagocytosis of apoptotic cells, and there existed the key cytoplasmic domain for signal transduction...
July 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28754799/the-nonreceptor-protein-tyrosine-kinase-pyk2-promotes-the-turnover-of-monocytes-at-steady-state
#9
Ryan A Llewellyn, Keena S Thomas, Michael F Gutknecht, Amy H Bouton
Monocytes are short-lived myeloid cells that perform functions essential for tissue homeostasis and disease resolution. However, the cellular mechanisms controlling the maintenance and turnover of monocyte populations are largely undefined. Proline-rich tyrosine kinase 2 (Pyk2) is a nonreceptor tyrosine kinase that regulates numerous immune cell functions, but its role in monocytes is currently unknown. In this study, we sought to characterize the expression and function of Pyk2 in lineage-committed monocyte populations...
July 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28754798/frontline-science-cxcr7-mediates-cd14-cd16-monocyte-transmigration-across-the-blood-brain-barrier-a-potential-therapeutic-target-for-neuroaids
#10
Mike Veenstra, Dionna W Williams, Tina M Calderon, Kathryn Anastos, Susan Morgello, Joan W Berman
CD14(+)CD16(+) monocytes transmigrate into the CNS of HIV-positive people in response to chemokines elevated in the brains of infected individuals, including CXCL12. Entry of these cells leads to viral reservoirs, neuroinflammation, and neuronal damage. These may eventually lead to HIV-associated neurocognitive disorders. Although antiretroviral therapy (ART) has significantly improved the lives of HIV-infected people, the prevalence of cognitive deficits remains unchanged despite ART, still affecting >50% of infected individuals...
July 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28754797/elastase-inhibitors-as-potential-therapies-for-elane-associated-neutropenia
#11
Vahagn Makaryan, Merideth L Kelley, Breanna Fletcher, Audrey Anna Bolyard, Andrew Aprikyan, David C Dale
Mutations in ELANE, the gene for neutrophil elastase (NE), a protease expressed early in neutrophil development, are the most frequent cause of cyclic (CyN) and severe congenital neutropenia (SCN). We hypothesized that inhibitors of NE, acting either by directly inhibiting enzymatic activity or as chaperones for the mutant protein, might be effective as therapy for CyN and SCN. We investigated β-lactam-based inhibitors of human NE (Merck Research Laboratories, Kenilworth, NJ, USA), focusing on 1 inhibitor called MK0339, a potent, orally absorbed agent that had been tested in clinical trials and shown to have a favorable safety profile...
July 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28751473/identification-of-the-macrophage-specific-promoter-signature-in-fantom5-mouse-embryo-developmental-time-course-data
#12
Kim M Summers, David A Hume
The FANTOM5 consortium used cap analysis of gene expression (CAGE) to analyze the time course of gene expression over development from 11 days postcoitum (dpc) to adult in 16 developing organs and the whole body of the mouse. Every tissue in the body contains a large number of resident macrophages that initially infiltrate the embryo from the yolk sac. These cells contribute to organogenesis, and their functions diversify during development as they acquire tissue-specific adaptations. In each of the FANTOM5 time courses, the expression of known macrophage-specific genes, including CSF1 receptor (Csf1r), epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (Emr1), and mer receptor tyrosine kinase (Mertk), was readily detectable and increased with time...
July 27, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28751472/parkinson-disease-associated-lrrk2-g2019s-transgene-disrupts-marrow-myelopoiesis-and-peripheral-th17-response
#13
Jeongho Park, Jang-Won Lee, Scott C Cooper, Hal E Broxmeyer, Jason R Cannon, Chang H Kim
Parkinson's disease (PD) is a neurodegenerative disease, whereas Crohn's disease is an inflammatory bowel disease. Interestingly, polymorphisms in the LRRK2 gene have been identified as risk factors for both diseases. LRRK2 G2019S is the most prevalent mutation found in PD. To gain insights into the role of the LRRK2 G2019S gene on the development and activation of the immune system in the brain-gut axis, we investigated the effect of LRRK2 G2019S on bone marrow myeloid progenitors and myeloid cell function in the periphery...
July 27, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28747319/frontline-science-a-hyporesponsive-subset-of-rat-nk-cells-negative-for-ly49s3-and-nkr-p1b-are-precursors-to-the-functionally-mature-nkr-p1b-subset
#14
Amanda Sudworth, John T Vaage, Marit Inngjerdingen, Lise Kveberg
Rat NK cells are divided into major subsets expressing either Ly49 receptors or the inhibitory NKR-P1B receptor in conjunction with NKG2A/C/E receptors. A minor subset of NKp46(+) cells lacking expression of both Ly49 receptors and NKR-P1B is present in blood and spleen and is associated with decreased functional competence. We hypothesized that this subset may represent precursors to Ly49(+) and/or NKR-P1B(+) NK cells. When cultured in vitro in IL-2 and IL-15 or adoptively transferred to syngeneic hosts, a portion of NKR-P1B (-) Ly49s3 (-) cells transformed to express NKR-P1B, but very little Ly49s3...
July 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28733463/tlr4-and-c5ar-crosstalk-in-dendritic-cells-induces-a-core-regulatory-network-of-rsk2-pi3k%C3%AE-sgk1-and-foxo-transcription-factors
#15
Anouk Zaal, Benjamin Nota, Kat S Moore, Miranda Dieker, S Marieke van Ham, Anja Ten Brinke
Crosstalk between complement component 5a receptors (C5aRs) and TLRs in dendritic cells (DCs) occurs upon pathogen invasion; however, studies on C5aR and TLR crosstalk mainly focused on the modulating effect of C5a on TLR-induced cytokine production. To elucidate the breadth of C5aR and TLR4 crosstalk, the effect of simultaneous treatment with C5a and LPS was investigated in human monocyte-derived DCs (moDCs) 2 h after stimulation using whole transcriptome sequencing analysis. Although the effect of C5a on hallmark genes defining TLR4-induced DC maturation was limited at this time point, RNA sequencing analysis revealed a great variety of novel C5a targets, of which many interfere with TLR4-mediated immune activation...
July 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28733462/human-t-cell-immunosenescence-and-inflammation-in-aging
#16
REVIEW
Arsun Bektas, Shepherd H Schurman, Ranjan Sen, Luigi Ferrucci
The aging process is driven by a finite number of inter-related mechanisms that ultimately lead to the emergence of characteristic phenotypes, including increased susceptibility to multiple chronic diseases, disability, and death. New assays and analytical tools have become available that start to unravel some of these mechanisms. A prevailing view is that aging leads to an imbalance between stressors and stress-buffering mechanisms that causes loss of compensatory reserve and accumulation of unrepaired damage...
July 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28729360/potential-role-of-cyclophilin-a-in-regulating-cytokine-secretion
#17
REVIEW
Farman Ullah Dawar, Yang Xiong, Muhammad Nasir Khan Khattak, Jun Li, Li Lin, Jie Mei
Cyclophilin A (CypA), a peptidylprolyl cis-trans isomerase, is a ubiquitous and multifunctional protein. In addition to its role as a host-cell receptor for cyclosporine A, CypA has diverse functions in inflammatory conditions and diseases. CypA secreted in response to inflammatory stimuli binds to the cell surface via its receptor CD147 and induces secretion of various inflammatory cytokines. However, silencing and inhibition of either CypA or CD147 inhibits inflammatory cytokine expression and inflammation...
July 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28729359/the-%C3%AE-defensin-retrocyclin-101-inhibits-tlr4-and-tlr2-dependent-signaling-and-protects-mice-against-influenza-infection
#18
Daniel Prantner, Kari Ann Shirey, Wendy Lai, Wuyuan Lu, Alexander M Cole, Stefanie N Vogel, Alfredo Garzino-Demo
Despite widespread use of annual influenza vaccines, seasonal influenza-associated deaths number in the thousands each year, in part because of exacerbating bacterial superinfections. Therefore, discovering additional therapeutic options would be a valuable aid to public health. Recently, TLR4 inhibition has emerged as a possible mechanism for protection against influenza-associated lethality and acute lung injury. Based on recent data showing that rhesus macaque θ-defensins could inhibit TLR4-dependent gene expression, we tested the hypothesis that a novel θ-defensin, retrocyclin (RC)-101, could disrupt TLR4-dependent signaling and protect against viral infection...
July 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28729358/targeting-c-type-lectin-receptors-a-high-carbohydrate-diet-for-dendritic-cells-to-improve-cancer-vaccines
#19
REVIEW
Dieke van Dinther, Dorian A Stolk, Rieneke van de Ven, Yvette van Kooyk, Tanja D de Gruijl, Joke M M den Haan
There is a growing understanding of why certain patients do or do not respond to checkpoint inhibition therapy. This opens new opportunities to reconsider and redevelop vaccine strategies to prime an anticancer immune response. Combination of such vaccines with checkpoint inhibitors will both provide the fuel and release the brake for an efficient anticancer response. Here, we discuss vaccine strategies that use C-type lectin receptor (CLR) targeting of APCs, such as dendritic cells and macrophages. APCs are a necessity for the priming of antigen-specific cytotoxic and helper T cells...
July 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28724696/is-leukostasis-a-crucial-step-or-epiphenomenon-in-the-pathogenesis-of-diabetic-retinopathy
#20
REVIEW
Anne-Eva van der Wijk, John M Hughes, Ingeborg Klaassen, Cornelis J F Van Noorden, Reinier O Schlingemann
Leukostasis in the retinal microvasculature in animal model studies of diabetes is associated with the development of diabetes-like retinopathy. Therefore, it is generally assumed that adhesion of leukocytes is a central event inciting a chronic, low-grade form of inflammation that causes the vascular abnormalities that are specific for the early stages of diabetic retinopathy (DR), which culminate in diabetic macular edema, proliferative DR, and vision loss in humans. Here, we review the literature critically with respect to leukostasis and assess its pathologic consequences in the human diabetic retina...
July 19, 2017: Journal of Leukocyte Biology
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