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Journal of Leukocyte Biology

Usharani Talla, Stephanie M Bozonet, Heather A Parker, Mark B Hampton, Margreet C M Vissers
Neutrophils contribute to low oxygen availability at inflammatory sites through the generation of reactive oxidants. They are also functionally affected by hypoxia, which delays neutrophil apoptosis. However, the eventual fate of neutrophils in hypoxic conditions is unknown and this is important for their effective clearance and the resolution of inflammation. We have monitored the survival and function of normal human neutrophils exposed to hypoxia over a 48 h period. Apoptosis was delayed, and the cells remained intact even at 48 h...
August 14, 2019: Journal of Leukocyte Biology
Katharine M Irvine, Melanie Caruso, Michelle Ferrari Cestari, Gemma M Davis, Sahar Keshvari, Anuj Sehgal, Clare Pridans, David A Hume
Macrophages are present in large numbers in every tissue in the body where they play critical roles in development and homeostasis. They exhibit remarkable phenotypic and functional diversity, underpinning their adaptation to specialized roles in each tissue niche. CSF1, signaling through the CSF1 receptor, which is restricted to monocyte-macrophage lineage cells in adults, is a critical growth factor controlling macrophage proliferation, differentiation, and many aspects of mature macrophage function. We have generated a macrophage reporter rat, utilizing a construct containing elements of the mouse Csf1r promoter and the highly conserved Fms intronic regulatory element to drive mApple fluorescent protein expression...
August 8, 2019: Journal of Leukocyte Biology
Yutaka Kondo, Carola Ledderose, Christian J Slubowski, Mahtab Fakhari, Yuka Sumi, Koichiro Sueyoshi, Ann-Katrin Bezler, Dilan Aytan, Mona Arbab, Wolfgang G Junger
Bacterial infections and sepsis are leading causes of morbidity and mortality in critically ill patients. Currently, there are no effective treatments available to improve clinical outcome in sepsis. Here, we elucidated a mechanism by which Escherichia coli (E. coli) bacteria impair neutrophil (PMN) chemotaxis and we studied whether this mechanism can be therapeutically targeted to improve chemotaxis and antimicrobial host defense. PMNs detect bacteria with formyl peptide receptors (FPR). FPR stimulation triggers mitochondrial ATP production and release...
August 8, 2019: Journal of Leukocyte Biology
Lívia D Tavares, Izabela Galvão, Vivian V Costa, Nathalia V Batista, Lívia C R Rossi, Camila B Brito, Alesandra C Reis, Celso M Queiroz-Junior, Amanda D Braga, Fernanda M Coelho, Ana C Dias, Dario S Zamboni, Vanessa Pinho, Mauro M Teixeira, Flávio A Amaral, Daniele G Souza
This study investigates the participation of PI3Kγ in the development of joint inflammation and dysfunction in an experimental model of acute gout in mice. Acute gout was induced by injection of monosodium urate (MSU) crystals into the tibiofemoral joint of mice. The involvement of PI3Kγ was evaluated using a selective inhibitor and mice deficient for PI3Kγ (PI3Kγ-/- ) or with loss of kinase activity. Neutrophils recovered from the inflamed joint were quantified and stained for phosphorylated Akt (pAkt) and production of reactive oxygen species (ROS)...
August 8, 2019: Journal of Leukocyte Biology
Ting Feng, Xuelian Liao, Xuewei Yang, Chuan Yang, Fang Lin, Yinkun Guo, Yan Kang, Hong Li
Most information about the immune status of NK cells during sepsis has been obtained from animal models, athough data from clinical septic patients is limited. In this study, we aimed to decipher NK cell immunity of septic patients in a more comprehensive way. We found that cytotoxicity of NK cells dramatically decreased during sepsis, likely due to the reduction of cluster of differentiation (CD)3- CD56+ NK cells and a shift of phenotypic changes of NK group 2 member (NKG2) receptors, natural cytotoxicity receptors (NCRs) and killer immunoglobulin-like receptors (KIRs) toward inhibitory receptors demonstrated by CD3- CD56+ NK cells in septic patients...
August 6, 2019: Journal of Leukocyte Biology
Melanie J Scott
No abstract text is available yet for this article.
August 5, 2019: Journal of Leukocyte Biology
John E Griepentrog, Xianghong Zhang, Anthony J Lewis, Gianmarino Gianfrate, Hanna E Labiner, Baobo Zou, Zeyu Xiong, Janet S Lee, Matthew R Rosengart
The wavelength of light is a critical determinant of light's capacity to entrain adaptive biological mechanisms, such as enhanced immune surveillance, that precede and prepare us for the active circadian day, a time when the risk of encountering pathogen is highest. Light rich in the shorter wavelength visible blue spectrum maximally entrains these circadian rhythms. We hypothesized that exposure to blue light during sepsis will augment immunity and improve outcome. Using a clinically relevant Klebsiella pneumoniae acute lower respiratory tract infection model, we show that blue spectrum light shifts autonomic tone toward parasympathetic predominance and enhances immune competence, as characterized by accelerated pathogen clearance that is accompanied by reduced alveolar neutrophil influx, inflammation, and improved survival...
August 4, 2019: Journal of Leukocyte Biology
Laura Labarthe, Soledad Henriquez, Olivier Lambotte, James P Di Santo, Roger Le Grand, Françoise Pflumio, Marie-Laure Arcangeli, Nicolas Legrand, Christine Bourgeois
This work sought to confirm the human-like expression of exhaustion and senescence markers in a mouse model with a humanized immune system (HIS): the Balb/c Rag2KO IL2rgcKO SirpαNOD Flk2KO HLA-A2HHD (BRGSF-A2) mouse reconstituted with human CD34+ cord blood cells. With regard to senescence markers, the percentage of CD57+ T cells was higher in the bone marrow (BM) than in the spleen or blood. The same was true for KLRG1+ hCD8+ T cells. With regard to exhaustion markers, the percentage of programmed death 1 (PD-1+ ) T cells was higher in the BM than in the spleen or blood; the same was true for TIGIT+ hCD4+ cells...
August 4, 2019: Journal of Leukocyte Biology
Valerie A C M Koeken, Ayesha J Verrall, Edwin Ardiansyah, Lika Apriani, Jéssica C Dos Santos, Vinod Kumar, Bachti Alisjahbana, Philip C Hill, Leo A B Joosten, Reinout van Crevel, Arjan van Laarhoven
Studies in IL-32 transgenic mice and in vitro suggest that IL-32 may have protective effects against Mycobacterium tuberculosis, but so far there are barely any studies in humans. We studied the role of IL-32 and its splice variants in tuberculosis (TB) in vivo and in vitro. Blood transcriptional analysis showed lower total IL-32 mRNA levels in pulmonary TB patients compared to patients with latent TB infection and healthy controls. Also, among Indonesian household contacts who were heavily exposed to an infectious TB patient, IL-32 mRNA levels were higher among those who remained uninfected compared to those who became infected with M...
August 4, 2019: Journal of Leukocyte Biology
Felipe A Pinho-Ribeiro
Discussion on the impact of blood leukocytes accumulating at the borders of the central nervous system on the development of neuropathic pain.
August 4, 2019: Journal of Leukocyte Biology
Ramasatyaveni Geesala, Priya D Issuree, Thorsten Maretzky
iRhoms are related to a family of intramembrane serine proteinases called rhomboids but lack proteolytic activity. In mammals, there are two iRhoms, iRhom1 and iRhom2, which have similar domain structures and overlapping specificities as well as distinctive functions. These catalytically inactive rhomboids are essential regulators for the maturation and trafficking of the disintegrin metalloprotease ADAM17 from the endoplasmic reticulum to the cell surface, and are required for the cleavage and release of a variety of membrane-associated proteins, including the IL-6 receptor, l-selectin, TNF, and EGFR ligands...
August 1, 2019: Journal of Leukocyte Biology
Luisa Menezes-Silva, Denise Morais da Fonseca
Discussion on changes in gut microbiota driving the breakdown of mucosal barrier in NOD mice; the resulting inflammation and impairment of oral tolerance induces the autoimmune diabetes.
August 1, 2019: Journal of Leukocyte Biology
Anna Ciesielska, Aneta Hromada-Judycka, Ewelina Ziemlińska, Katarzyna Kwiatkowska
Bacterial LPS strongly induces pro-inflammatory responses of Mϕs after binding to CD14 protein and the TLR4/MD-2 receptor complex. The LPS-triggered signaling can be modulated by extracellular lysophosphatidic acid (LPA), which is of substantial importance for Mϕ functioning under specific pathophysiological conditions, such as atherosclerosis. The molecular mechanisms of the crosstalk between the LPS- and LPA-induced signaling, and the LPA receptors involved, are poorly known. In this report, we show that LPA strongly inhibits the LPS-induced TNF-α production at the mRNA and protein levels in primary Mϕs and Mϕ-like J774 cells...
July 23, 2019: Journal of Leukocyte Biology
David A Hume, Melanie Caruso, Michelle Ferrari-Cestari, Kim M Summers, Clare Pridans, Katharine M Irvine
Mϕ proliferation, differentiation, and survival are controlled by signals from the Mϕ CSF receptor (CSF1R). Mono-allelic gain-of-function mutations in CSF1R in humans are associated with an autosomal-dominant leukodystrophy and bi-allelic loss-of-function mutations with recessive skeletal dysplasia, brain disorders, and developmental anomalies. Most of the phenotypes observed in these human disease states are also observed in mice and rats with loss-of-function mutations in Csf1r or in Csf1 encoding one of its two ligands...
July 22, 2019: Journal of Leukocyte Biology
Kelly Whittaker, Rob Burgess, Valerie Jones, Yanqing Yang, Weifan Zhou, Shuhong Luo, Jarad Wilson, Ruo-Pan Huang
This review discusses how the measurement of proteins in blood and its components via quantitative proteomics analyses can inform health status. Various external and internal factors such as environmental conditions, genetic background, nutrition, diet, and lifestyle, chronic pathological conditions, disease state, or therapeutic intervention will be investigated and their effects on the protein profile will be shown. The resulting changes to ones' health and how this protein expression information can be used in early screening/diagnostic applications, drug discovery, precision treatment, patient management, and monitoring overall health status will also be presented...
July 22, 2019: Journal of Leukocyte Biology
Fernanda P B Nunes, Ricardo Wesley Alberca-Custódio, Eliane Gomes, Denise M Fonseca, Nicole H Yokoyama, Alexis Labrada, Momtchilo Russo
Blomia tropicalis mite is highly prevalent in tropical and subtropical regions and it is associated with allergic diseases such as rhinitis and asthma. By using an OVA-model of allergic lung disease, we have previously shown that sensitization in the presence of toll like receptors (TLRs) agonists attenuates subsequent OVA-induced allergic responses. Here, we evaluated the effect of CpG-ODN, a specific synthetic TLR-9 agonist, on the development of experimental asthma induced by Blomia tropicalis extract, a relevant source of aeroallergens...
July 22, 2019: Journal of Leukocyte Biology
Bridget Mooney, Fernando J Torres-Velez, Jennifer Doering, Dylan J Ehrbar, Nicholas J Mantis
Ricin toxin is a plant-derived, ribosome-inactivating protein that is rapidly cleared from circulation by Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs)-with fatal consequences. Rather than being inactivated, ricin evades normal degradative pathways and kills both KCs and LSECs with remarkable efficiency. Uptake of ricin by these 2 specialized cell types in the liver occurs by 2 parallel routes: a "lactose-sensitive" pathway mediated by ricin's galactose/N-acetylgalactosamine-specific lectin subunit (RTB), and a "mannose-sensitive" pathway mediated by the mannose receptor (MR; CD206) or other C-type lectins capable of recognizing the mannose-side chains displayed on ricin's A (RTA) and B subunits...
July 16, 2019: Journal of Leukocyte Biology
Elisa Gremese, Stefano Alivernini, Barbara Tolusso, Martin P Zeidler, Gianfranco Ferraccioli
Methotrexate (MTX) is recognized as the anchor drug in the algorithm treating chronic arthritis (RA, psoriatic arthritis), as well as a steroid sparing agent in other inflammatory conditions (polymyalgia rheumatica, vasculitis, scleroderma). Its main mechanism of action has been related to the increase in extracellular adenosine, which leads to the effects of A2A receptor in M1 macrophages that dampens TNFα and IL12 production and increases IL1Ra and TNFRp75. By acting on A2B receptor on M2 macrophages it enhances IL10 synthesis and inhibits NF-kB signaling...
July 16, 2019: Journal of Leukocyte Biology
Mariana Camila Gonçalves Miranda, Rafael Pires Oliveira, Lícia Torres, Sarah Leão Fiorini Aguiar, Natalia Pinheiro-Rosa, Luísa Lemos, Mauro Andrade Guimarães, Daniela Reis, Tatiany Silveira, Ênio Ferreira, Thaís Garcias Moreira, Denise Carmona Cara, Tatiani Uceli Maioli, Brian L Kelsall, Daniela Carlos, Ana Maria Caetano Faria
Alterations in the composition of the intestinal microbiota have been associated with development of type 1 diabetes (T1D), but little is known about changes in intestinal homeostasis that contribute to disease pathogenesis. Here, we analyzed oral tolerance induction, components of the intestinal barrier, fecal microbiota, and immune cell phenotypes in non-obese diabetic (NOD) mice during disease progression compared to non-obese diabetes resistant (NOR) mice. NOD mice failed to develop oral tolerance and had defective protective/regulatory mechanisms in the intestinal mucosa, including decreased numbers of goblet cells, diminished mucus production, and lower levels of total and bacteria-bound secretory IgA, as well as an altered IEL profile...
July 16, 2019: Journal of Leukocyte Biology
Mahdis Monajemi, Shera Fisk, Yvonne C F Pang, Jessica Leung, Susan C Menzies, Rym Ben-Othman, Bing Cai, Tobias R Kollmann, Jacob Rozmus, Laura M Sly
This study tested the hypothesis that mucosa associated lymphoid tissue 1 (Malt1) deficiency causes osteoporosis in mice by increasing osteoclastogenesis and osteoclast activity. A patient with combined immunodeficiency (CID) caused by MALT1 deficiency had low bone mineral density resulting in multiple low impact fractures that was corrected by hematopoietic stem cell transplant (HSCT). We have reported that Malt1 deficient Mϕs, another myeloid cell type, are hyper-responsive to inflammatory stimuli. Our objectives were to determine whether Malt1 deficient mice develop an osteoporosis-like phenotype and whether it was caused by Malt1 deficiency in osteoclasts...
July 16, 2019: Journal of Leukocyte Biology
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