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Journal of Leukocyte Biology

Kim L Weisgrau, Logan J Vosler, Nicholas L Pomplun, Jennifer M Hayes, Heather A Simmons, Kristen R Friedrichs, Eva G Rakasz
Captive-bred rhesus macaques of Indian origin represent one of the most important large animal models for infectious disease, solid organ transplantation, and stem cell research. There is a dearth of information defining hematopoietic development, including neutrophil leukocyte differentiation in this species using multicolor flow cytometry. In the current study, we sought to identify cell surface markers that delineate neutrophil progenitor populations with characteristic immunophenotypes. We defined four different postmitotic populations based on their CD11b and CD87 expression pattern, and further refined their immunophenotypes using CD32, CD64, lactoferrin, and myeloperoxidase as antigenic markers...
November 5, 2018: Journal of Leukocyte Biology
Dounia Chraa, Asmaa Naim, Daniel Olive, Abdallah Badou
Although immune-based therapy is proving to be a success in several cancer types, only a set of patients appear to respond to immune checkpoint blockade including PD-1 and CTLA-4. A better understanding of the crucial components of cancer immunity is therefore necessary. T lymphocytes, a key element, are found within the tumor microenvironment and seem to be critical in determining the efficacy of immune surveillance. In this review, we will depict the pro- and antitumor roles of major T cell subsets in distinct cancer tissues...
November 2, 2018: Journal of Leukocyte Biology
Laura E Collins, Linda Troeberg
Heparan sulfate is found on the surface of most cell types, as well as in basement membranes and extracellular matrices. Its strong anionic properties and highly variable structure enable this glycosaminoglycan to provide binding sites for numerous protein ligands, including many soluble mediators of the immune system, and may promote or inhibit their activity. The formation of ligand binding sites on heparan sulfate (HS) occurs in a tissue- and context-specific fashion through the action of several families of enzymes, most of which have multiple isoforms with subtly different specificities...
October 30, 2018: Journal of Leukocyte Biology
Erika Ricci, Simona Ronchetti, Elena Gabrielli, Eva Pericolini, Marco Gentili, Elena Roselletti, Anna Vecchiarelli, Carlo Riccardi
Glucocorticoid-induced leucine zipper (GILZ) exerts anti-inflammatory effects on the immune cells. However, less is known about GILZ function in neutrophils. We aimed to define the specific role of GILZ in basal neutrophil activity during an inflammatory response. GILZ knockdown resulted in a persistent activation state of neutrophils, as evidenced by increased phagocytosis, killing activity, and oxidative burst in GILZ-knockout (KO) neutrophils. This enhanced response caused severe disease in a dinitrobenzene sulfonic acid (DNBS)-induced colitis model, where GILZ-KO mice had prominent granulocytic infiltrate and excessive inflammatory state...
October 29, 2018: Journal of Leukocyte Biology
Agustina M Pino-Martínez, Cristian G Miranda, Estela I Batalla, Stella M González-Cappa, Catalina D Alba Soto
IL-10 is a pleiotropic cytokine with immunoregulatory functions affecting various cell types. In a model of experimental infection with the protozoan Trypanosoma cruzi (T. cruzi), we found increased morbidity and lower parasite control in IL-10 deficient mice (IL-10 KO) compared to wild-type (WT) mice. Despite enhanced Mϕ function and dendritic cell activation, IL-10 KO mice were more susceptible to infection. The kinetics of T cells in spleen and peripheral blood revealed that infected IL-10 KO mice failed to increase the number of spleen and circulating total CD8+ T cells, a phenomenon observed from the second week of infection in WT mice...
October 29, 2018: Journal of Leukocyte Biology
Jia Zhou, Junru Li, Yu Yu, Yan Liu, Huifang Li, Yunzhi Liu, Jun Wang, Liyun Zhang, Xiao Lu, Zhengliang Chen, Daming Zuo
Noninfectious liver injury, including the effects of drugs and diet, is a major cause of liver diseases worldwide. The innate inflammatory response to hepatocyte death plays a crucial role in the outcome of liver injury. Mannan-binding lectin (MBL) is a pattern recognition molecule of the innate immune system, which is primarily produced by liver. MBL deficiency occurs with high frequency in the population and is reported associated with predisposition to infectious diseases. We here observed that genetic MBL ablation strongly sensitizes mice to sterile liver injury induced by carbon tetrachloride (CCl4 )...
October 23, 2018: Journal of Leukocyte Biology
Fadoua Belaiba, Imene Medimegh, Meriem Ammar, Feriel Jemni, Amel Mezlini, Khaled Ben Romdhane, Lotfi Cherni, Amel Benammar Elgaaïed
Micro-RNAs (miRs) constitute a class of small noncoding RNAs implicated in the regulation of gene expression by binding to target mRNAs. A miR can target several mRNAs, being involved in different biologic processes and pathologies. This pleiotropic function might explain the link between diseases co-occurrence. Epigenetic origin of the link between obesity and breast cancer (BC) is investigated in a cohort of Tunisian patients, focusing on polymorphism at germline level (miR-146a) and on expression in mammary tumors (miR-21, miR-146a, and miR-34a), according to body mass index (BMI) and clinico-pathologic features...
October 10, 2018: Journal of Leukocyte Biology
Raphaela Schwentner, Gunhild Jug, Maximilian O Kauer, Thomas Schnöller, Petra Waidhofer-Söllner, Wolfgang Holter, Caroline Hutter
Langerhans cell histiocytosis (LCH) is a MAPK pathway-driven disease characterized by the accumulation of CD1a+ langerin+ cells of unknown origin. We have previously reported that the Notch signaling pathway is active in LCH lesions and that the Notch ligand Jagged2 (JAG2) induces CD1a and langerin expression in monocytes in vitro. Here we show that Notch signaling induces monocytes to acquire an LCH gene signature and that Notch inhibition suppresses the LCH phenotype. In contrast, while also CD1c+ dendritic cells or IL-4-stimulated CD14+ monocytes acquire CD1a and langerin positivity in culture, their gene expression profiles and surface phenotypes are more different from primary LCH cells...
October 8, 2018: Journal of Leukocyte Biology
Damien Bierschenk, Mercedes Monteleone, Fiona Moghaddas, Paul J Baker, Seth L Masters, Dave Boucher, Kate Schroder
Inflammasomes are signaling hubs that activate inflammatory caspases to drive cytokine maturation and cell lysis. Inflammasome activation by Salmonella Typhimurium infection or Salmonella-derived molecules is extensively studied in murine myeloid cells. Salmonella-induced inflammasome signaling in human innate immune cells, is however, poorly characterized. Here, we show that Salmonella mutation to inactivate the Salmonella pathogenicity island-2 type III secretion system (SPI2 T3SS) potentiates S. Typhimurium-induced inflammasome responses from primary human macrophages, resulting in strong IL-1β production and macrophage death...
October 4, 2018: Journal of Leukocyte Biology
Caroline M Percopo, Julia O Krumholz, Elizabeth R Fischer, Laura S Kraemer, Michelle Ma, Karen Laky, Helene F Rosenberg
Eosinophil peroxidase (EPX) is a major constituent of the large cytoplasmic granules of both human and mouse eosinophilic leukocytes. Human EPX deficiency is a rare, autosomal-recessive disorder limited to the eosinophil lineage. Our intent was to explore the impact of EPX gene deletion on eosinophil content, structure, and function. In response to repetitive intranasal challenge with a filtrate of the allergen, Alternaria alternata, we found significantly fewer eosinophils peripherally and in the respiratory tracts of EPX-/- mice compared to wild-type controls; furthermore, both the major population (Gr1-/lo ) and the smaller population of Gr1hi eosinophils from EPX-/- mice displayed lower median fluorescence intensities (MFIs) for Siglec F...
October 4, 2018: Journal of Leukocyte Biology
Rashmi Saini, Sarika Singh
Neutrophils play a key role in innate immune responses against foreign intrusion and influence the subsequent instigation of adaptive immune response. Nitric oxide (NO) synthesized by neutrophil nitric oxide synthase (NOS) profoundly modulates their diverse physiological responsibilities furthermore encompassing pathological implications. Neutrophils are the active participants in diverse inflammatory and cardiovascular disorders but neutrophil nitric oxide synthase (NOS) remains enigmatic on various aspects...
October 4, 2018: Journal of Leukocyte Biology
Chuan Yang, Chongyang Shen, Ting Feng, Hong Li
Noncoding RNAs (ncRNA) are important regulators that modulate cell proliferation, apoptosis, the cell cycle, and DNA methylation. NK cells mediate the immune response via the secretion of various cytokines and are important innate immune cells in the human immune system. Recent studies have found that ncRNA plays an important role in NK cell development and function. With recent advances in bioinformatics and next-generation sequencing, novel ncRNAs have been identified, allowing us to more fully appreciate its functions in NK cell biology...
September 28, 2018: Journal of Leukocyte Biology
Ulf Yrlid, Maricris Holm, Malin Levin, Samuel Alsén, Malin Lindbom, Lars Glise, Niklas Bergh, Jan Borén, Per Fogelstrand
Endothelial injury makes the vessel wall vulnerable to cardiovascular diseases. Injured endothelium regenerates by collective sheet migration, that is, the endothelial cells coordinate their motion and regrow as a sheet of cells with retained cell-cell contacts into the wounded area. Leukocytes appear to be involved in endothelial repair in vivo; however, little is known about their identity and role in the reparative sheet migration process. To address these questions, we developed a high-quality en face technique that enables visualizing of leukocytes and endothelial cells simultaneously following an endoluminal scratch wound injury of the mouse carotid artery...
September 28, 2018: Journal of Leukocyte Biology
Yanzhuo Liu, Honglin Tang, Xiaoxiao Liu, Honglei Chen, Na Feng, Jing Zhang, Chenlong Wang, Miao Qiu, Jing Yang, Xiaoyang Zhou
Cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and cytochrome P450 (CYP) 4A-mediated arachidonic acid (AA) metabolism play an essential role in human inflammatory disorders. Blocking COX-2 pathway would shunt AA metabolism to the other pathway, thereby decreasing the efficacy and exacerbating adverse effects. Here we demonstrated that reprogramming COX-2, 5-LOX, and CYP4A-mediated AA metabolism in macrophages by salidroside (Sal) ameliorates monosodium urate (MSU) crystal-induced inflammation. Compared with COX-2 inhibitor celecoxib, Sal (80 mg/kg) presented a superior anti-arthritic profile in MSU crystal-treated rats, accompanied with the decreased expression of COX-2, 5-LOX, and CYP4A and production of prostaglandin E2 (PGE2 ), leukotriene B4 (LTB4 ), and 20-hydroxyeicosatetraenoic acid (20-HETE) in the synovial fluid macrophages...
September 28, 2018: Journal of Leukocyte Biology
Mathew A Huggins, Stephen C Jameson, Sara E Hamilton
Research using mouse models have contributed essential knowledge toward our current understanding of how the human immune system functions. One key difference between humans and typical laboratory mice, however, is exposure to pathogens in their respective environments. Several recent studies have highlighted that these microbial encounters shape the development and functional status of the immune system. For humans, such numerous and unavoidable encounters with viruses, bacteria, and parasites may be a defining factor in generating a healthy and robust immune system, poised to respond to new infections and to vaccination...
September 27, 2018: Journal of Leukocyte Biology
Chantal Donovan, Malcolm R Starkey, Richard Y Kim, Batika M J Rana, Jillian L Barlow, Bernadette Jones, Tatt Jhong Haw, Prema Mono Nair, Kurtis Budden, Guy J M Cameron, Jay C Horvat, Peter A Wark, Paul S Foster, Andrew N J McKenzie, Philip M Hansbro
Pulmonary inflammation in chronic obstructive pulmonary disease (COPD) is characterized by both innate and adaptive immune responses; however, their specific roles in the pathogenesis of COPD are unclear. Therefore, we investigated the roles of T and B lymphocytes and group 2 innate lymphoid cells (ILC2s) in airway inflammation and remodelling, and lung function in an experimental model of COPD using mice that specifically lack these cells (Rag1-/- and Rorafl/fl Il7rCre [ILC2-deficient] mice). Wild-type (WT) C57BL/6 mice, Rag1-/- , and Rorafl/fl Il7rCre mice were exposed to cigarette smoke (CS; 12 cigarettes twice a day, 5 days a week) for up to 12 weeks, and airway inflammation, airway remodelling (collagen deposition and alveolar enlargement), and lung function were assessed...
September 27, 2018: Journal of Leukocyte Biology
Katherine R Balka, Dominic De Nardo
TLRs are expressed on the plasma and endosomal membranes of innate immune cells acting as sensors of foreign and inherent danger signals that threaten the host. Upon activation, TLRs facilitate the assembly of large intracellular oligomeric signaling complexes, termed Myddosomes, which initiate key signal transduction pathways to elicit critical inflammatory immune responses. The formation of the Myddosome is integral for TLR signaling; however, the molecular mechanisms controlling its formation, disassembly, and the subsequent proximal signaling events remain to be clearly defined...
September 26, 2018: Journal of Leukocyte Biology
Hushan Zhang, Zhiming Wang, Ronghua Liu, Tingting Qian, Jiajing Liu, Luman Wang, Yiwei Chu
Reactive oxygen species (ROS) are electrophilic chemical species produced from incomplete oxidation. They have long been known as aggressive molecules that lead to direct tissue and cellular damage. Recent studies have reconsidered ROS as second messengers in the initiation and amplification of cell signaling, but how ROS regulate lung tissue and immune cell remain unknown. In this study, we used a LPS-induced acute lung injury (ALI) mouse model to observe disease, progression and determine ROS-related immune responses...
September 17, 2018: Journal of Leukocyte Biology
Luke C Davies, Christopher M Rice, Daniel W McVicar, Jonathan M Weiss
Phagocytes are cells of the immune system that play important roles in phagocytosis, respiratory burst and degranulation-key components of innate immunity and response to infection. This diverse group of cells includes monocytes, macrophages, dendritic cells, neutrophils, eosinophils, and basophils-heterogeneous cell populations possessing cell and tissue-specific functions of which cellular metabolism comprises a critical underpinning. Core functions of phagocytic cells are diverse and sensitive to alterations in environmental- and tissue-specific nutrients and growth factors...
September 14, 2018: Journal of Leukocyte Biology
Rym Ouni, Houda Gharsalli, Violette Dirix, Amani Braiek, Nadia Sendi, Afifa Jarraya, Leila Douik El Gharbi, Mohamed-Ridha Barbouche, Chaouki Benabdessalem
Nearly two billion people are latently infected with Mtb (LTBI). Detection of LTBI with high risk to develop active tuberculosis (aTB) is considered the cornerstone to control the disease. The current challenge is to identify markers that better classify LTBI versus aTB. It has been previously shown that Rv0140, a reactivation-associated antigen of Mtb, induces significantly higher IFN-γ production in LTBI individuals as compared to aTB patients. Herein, we show that Rv0140 induces high granzyme B level by PBMCs derived from LTBI (n = 34) as compared to aTB (n = 18)...
September 13, 2018: Journal of Leukocyte Biology
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