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Journal of Leukocyte Biology

Abigail R Cannon, Paulius V Kuprys, Adrienne N Cobb, Xianzhong Ding, Anai N Kothari, Paul C Kuo, Joshua M Eberhardt, Adam M Hammer, Niya L Morris, Xiaoling Li, Mashkoor A Choudhry
Over 1.4 million Americans have been diagnosed with inflammatory bowel disease (IBD), and ulcerative colitis (UC) makes up approximately half of those diagnoses. As a disease, UC cycles between periods of remission and flare, which is characterized by intense abdominal pain, increased weight loss, intestinal inflammation, rectal bleeding, and dehydration. Interestingly, a widespread recommendation to IBD patients for avoidance of a flare period is "Don't Drink Alcohol" as recent work correlated alcohol consumption with increased GI symptoms in patients with IBD...
May 18, 2018: Journal of Leukocyte Biology
Samuel Philip Nobs, Manfred Kopf
The transcription factor PPAR-γ (peroxisome proliferator-activated receptor-γ) is a key regulator of lung immunity exhibiting multiple cell type specific roles in controlling development and function of the lung immune system. It is strictly required for the generation of alveolar macrophages by controlling differentiation of fetal lung monocyte precursors. Furthermore, it plays an important role in lung allergic inflammation by licensing lung dendritic cell t helper 2 (Th2) priming capacity as well as acting as a master transcription factor for pathogenic Th2 cells...
May 16, 2018: Journal of Leukocyte Biology
Astrid S Jørgensen, Pontian E Adogamhe, Julia M Laufer, Daniel F Legler, Christopher T Veldkamp, Mette M Rosenkilde, Gertrud M Hjortø
CCL19 is more potent than CCL21 in inducing chemotaxis of human dendritic cells (DC). This difference is attributed to 1) a stronger interaction of the basic C-terminal tail of CCL21 with acidic glycosaminoglycans (GAGs) in the environment and 2) an autoinhibitory function of this C-terminal tail. Moreover, different receptor docking modes and tissue expression patterns of CCL19 and CCL21 contribute to fine-tuned control of CCR7 signaling. Here, we investigate the effect of the tail of CCL21 on chemokine binding to GAGs and on CCR7 activation...
May 16, 2018: Journal of Leukocyte Biology
Robert J Canter, Catherine T Le, Johanna M T Beerthuijzen, William J Murphy
Immunotherapy has achieved breakthrough status in many advanced stage malignancies and is rapidly becoming the fourth arm of cancer treatment. Although cancer immunotherapy has generated significant excitement because of the potential for complete and sometimes durable responses, there is also the potential for severe and occasionally life-threatening toxicities, including cytokine release syndrome and severe autoimmunity. A large body of work also points to a "metainflammatory" state in obesity associated with impairment of immune responses...
May 15, 2018: Journal of Leukocyte Biology
Kirsten A Fairfax, Jessica E Bolden, Aaron J Robinson, Erin C Lucas, Tracey M Baldwin, Kerry A Ramsay, Rebecca Cole, Douglas J Hilton, Carolyn A de Graaf
Eosinophils are important in fighting parasitic infections and are implicated in the pathogenesis of asthma and allergy. IL-5 is a critical regulator of eosinophil development, controlling proliferation, differentiation, and maturation of the lineage. Mice that constitutively express IL-5 have in excess of 10-fold more eosinophils in the hematopoietic organs than their wild type (WT) counterparts. We have identified that much of this expansion is in a population of Siglec-F high eosinophils, which are rare in WT mice...
May 14, 2018: Journal of Leukocyte Biology
Jillian O Grace, Astha Malik, Hadar Reichman, Ariel Munitz, Artem Barski, Patricia C Fulkerson
The eosinophil (Eos) surface phenotype and activation state is altered after recruitment into tissues and after exposure to pro-inflammatory cytokines. In addition, distinct Eos functional subsets have been described, suggesting that tissue-specific responses for Eos contribute to organ homeostasis. Understanding the mechanisms by which Eos subsets achieve their tissue-specific identity is currently an unmet goal for the eosinophil research community. Publicly archived expression data can be used to answer original questions, test and generate new hypotheses, and serve as a launching point for experimental design...
May 14, 2018: Journal of Leukocyte Biology
Rossana C N Melo, Peter F Weller
Eosinophil secretory (specific) granules have a unique morphology and are both a morphologic hallmark of eosinophils and fundamental to eosinophil-mediated responses. Eosinophil mediators with multiple functional activities are presynthesized and stored within these granules, poised for very rapid, stimulus-induced secretion. The structural organization and changes of eosinophil specific granules are revealing in demonstrating the complex and diverse secretory activities of this cell. Here, we review our current knowledge on the architecture, composition, and function of eosinophil specific granules as highly elaborated organelles able to produce vesiculotubular carriers and to interplay with the intracellular vesicular trafficking...
May 11, 2018: Journal of Leukocyte Biology
Goutham Pattabiraman, Michael Murphy, Federica Agliano, Keaton Karlinsey, Andrei E Medvedev
IL-1 receptor-associated kinase (IRAK) 4 is a central enzyme of the TLR pathways. This study tested the hypothesis that IRAK4 kinase activity is prerequisite for regulating innate immunity during infections with intracellular bacteria. To this end, we analyzed responses of macrophages obtained from mice expressing wild-type (WT) IRAK4 or its kinase-inactive K213M mutant (IRAK4KI ) upon infection with intracellular bacteria Listeria monocytogenes or Mycobacterium smegmatis. In contrast to robust induction of cytokines by macrophages expressing kinase-sufficient IRAK4, IRAK4KI macrophages expressed decreased TNF-α, IL-6, IL-1β, and C-C motif chemokine ligand 5 upon infection with L...
May 11, 2018: Journal of Leukocyte Biology
Suin Jo, Hye-Ran Kim, YeVin Mun, Chang-Duk Jun
Transgelin-2 is a small 22-kDa actin-binding protein implicated in actin dynamics, which stabilizes actin structures and participates in actin-associated signaling pathways. Much curiosity regarding transgelin-2 has centered around its dysregulation in tumor development and associated diseases. However, recent studies have shed new light on the functions of transgelin-2, the only transgelin family member present in leukocytes, in the context of various immune responses. In this review, we outlined the biochemical properties of transgelin-2 and its physiological functions in T cells, B cells, and macrophages...
May 11, 2018: Journal of Leukocyte Biology
L Barington, F Wanke, K Niss Arfelt, P J Holst, F C Kurschus, M M Rosenkilde
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 receptors, EBI2 plays important roles in controlling the migration of immune cells during the course of a T-dependent Ab response in the spleen. In recent years, it has become clear that EBI2 also has other roles to play in the immune system...
May 9, 2018: Journal of Leukocyte Biology
Osric A Forrest, Sarah A Ingersoll, Marcela K Preininger, Julie Laval, Dominique H Limoli, Milton R Brown, Frances E Lee, Brahmchetna Bedi, Ruxana T Sadikot, Joanna B Goldberg, Vin Tangpricha, Amit Gaggar, Rabindra Tirouvanziam
RATIONALE: Recruitment of neutrophils to the airways, and their pathological conditioning therein, drive tissue damage and coincide with the loss of lung function in patients with cystic fibrosis (CF). So far, these key processes have not been adequately recapitulated in models, hampering drug development. Here, we hypothesized that the migration of naïve blood neutrophils into CF airway fluid in vitro would induce similar functional adaptation to that observed in vivo, and provide a model to identify new therapies...
May 9, 2018: Journal of Leukocyte Biology
Shida Yousefi, Satish K Sharma, Darko Stojkov, Nina Germic, Salome Aeschlimann, Moyar Q Ge, Cameron H Flayer, Erik D Larson, Imre G Redai, Suhong Zhang, Cynthia J Koziol-White, Katalin Karikó, Hans-Uwe Simon, Angela Haczku
The asthmatic airways are highly susceptible to inflammatory injury by air pollutants such as ozone (O3 ), characterized by enhanced activation of eosinophilic granulocytes and a failure of immune protective mechanisms. Eosinophil activation during asthma exacerbation contributes to the proinflammatory oxidative stress by high levels of nitric oxide (NO) production and extracellular DNA release. Surfactant protein-D (SP-D), an epithelial cell product of the airways, is a critical immune regulatory molecule with a multimeric structure susceptible to oxidative modifications...
May 7, 2018: Journal of Leukocyte Biology
Daiane Boff, Helena Crijns, Rik Janssens, Vincent Vanheule, Gustavo B Menezes, Soraia Macari, Tarcilia A Silva, Flavio A Amaral, Paul Proost
This study investigates if treatment with a peptide corresponding to the 30 C-terminal amino acids of CXCL9, CXCL9(74-103), ameliorates joint inflammation in a murine model of antigen-induced arthritis (AIA). AIA was induced in male C57BL/6J mice. Intravenous injection of CXCL9(74-103), simultaneously performed with a tibiofemoral challenge with methylated BSA (mBSA) as antigen in mice immunized with mBSA, diminished the accumulation of leukocytes, in particular neutrophils, in the synovial cavity. The levels of the chemokines CXCL1, CXCL2, and CXCL6 and of the cytokine IL-6 were decreased in inflamed periarticular tissue of mice treated with the CXCL9-derived peptide compared to non-treated AIA mice...
May 7, 2018: Journal of Leukocyte Biology
Charles Anthony Dinarello, Gilles Kaplanski
No abstract text is available yet for this article.
May 7, 2018: Journal of Leukocyte Biology
Federica M Marelli-Berg, Suchita Nadkarni
No abstract text is available yet for this article.
May 2, 2018: Journal of Leukocyte Biology
Laura Martínez-Muñoz, Ricardo Villares, José Luis Rodríguez-Fernández, José Miguel Rodríguez-Frade, Mario Mellado
The chemokines direct leukocyte recruitment in both homeostatic and inflammatory conditions, and are therefore critical for immune reactions. By binding to members of the class A G protein-coupled receptors, the chemokines play an essential role in numerous physiological and pathological processes. In the last quarter century, the field has accumulated much information regarding the implications of these molecules in different immune processes, as well as mechanistic insight into the signaling events activated through their binding to their receptors...
May 2, 2018: Journal of Leukocyte Biology
Kiyoshi Hirahara, Naoko Mato, Koichi Hagiwara, Toshinori Nakayama
The lungs are the primary organs of the respiratory system in many animals and have unique epithelial barrier systems to protect the host from continuous invasion of various harmful particles, such as viruses and bacteria. IL-33, a member of the IL-1 family of cytokines, is released from epithelial cells in the mucosal organs and drives the type 2 immune response by activating a number of immune cells in cases of helminth infection. However, IL-33 derived from epithelial cells also causes various allergic diseases via the activation of ST2-positive immune cells, including memory-type (CD62Llow CD44hi ) ST2+ CD4+ T cells in the lung...
April 30, 2018: Journal of Leukocyte Biology
Allison Rahtes, Shuo Geng, Christina Lee, Liwu Li
Inflammation is a host response to infection or damage and is vital for clearing pathogens and host debris. When this resolution fails to occur, chronic inflammation ensues. Chronic inflammation is typically characterized as a low-grade, persistent inflammatory process that can last for months or even years. This differs from acute inflammation, which is typically a fast, robust response to a stimulus followed by resolution with return to homeostasis. Inflammation resolution occurs through a variety of cellular processes and signaling components that act as "brakes" to keep inflammation in check...
April 24, 2018: Journal of Leukocyte Biology
Paneez Khoury, Praveen Akuthota, Steven J Ackerman, Joseph R Arron, Bruce S Bochner, Margaret H Collins, Jean-Emmanuel Kahn, Patricia C Fulkerson, Gerald J Gleich, Rashmi Gopal-Srivastava, Elizabeth A Jacobsen, Kristen M Leiferman, Levi-Schaffer Francesca, Sameer K Mathur, Michael Minnicozzi, Calman Prussin, Marc E Rothenberg, Florence Roufosse, Kathleen Sable, Dagmar Simon, Hans-Uwe Simon, Lisa A Spencer, Jonathan Steinfeld, Andrew J Wardlaw, Michael E Wechsler, Peter F Weller, Amy D Klion
BACKGROUND: Eosinophil-associated diseases (EADs) are rare, heterogeneous disorders characterized by the presence of eosinophils in tissues and/or peripheral blood resulting in immunopathology. The heterogeneity of tissue involvement, lack of sufficient animal models, technical challenges in working with eosinophils, and lack of standardized histopathologic approaches have hampered progress in basic research. Additionally, clinical trials and drug development for rare EADs are limited by the lack of primary and surrogate endpoints, biomarkers, and validated patient-reported outcomes...
April 19, 2018: Journal of Leukocyte Biology
Brett A Duguay, Kate Wei-Chen Huang, Marianna Kulka
Mast cells are important immune cells that have significant roles in mediating allergy and asthma. Therefore, studying the molecular mechanisms regulating these and other processes in mast cells is important to elucidate. Methods such as lipofection, transduction, and electroporation are often employed to dissect these mechanisms by disrupting gene expression in mast cell lines. However, as with other leukocytes, human mast cells (HMCs) are often refractory to the delivery of plasmids by lipofection. In this study, we investigated the utility of lipid nanoparticles (LNPs) containing the ionizable cationic lipids 1,2-dioleoyloxy-3-dimethylaminopropane, 1,2-dioleyloxy-3-dimethylaminopropane, or 2,2-dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane for the delivery of plasmid DNA into HMC lines...
April 18, 2018: Journal of Leukocyte Biology
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