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Journal of Leukocyte Biology | Page 2

Bénédicte Baïsse, Caroline Spertini, Frédérique Galisson, Tatiana Smirnova, Olivier Spertini
PSGL-1 is a mucin-like glycoprotein that supports, in mammals, leukocyte rolling on selectins. However, we have limited knowledge whether its function is conserved in non-mammals and how its structure adapted during evolution. To identify conserved amino acid sequences required for selectin binding, we performed multiple alignments of PSGL-1 sequences from 18 mammals, 4 birds, 3 reptiles, 1 amphibian, and 15 fishes. The amino-terminal T[D/E]PP[D/E] motif, which identifies in mammals a core-2 O-glycosylated threonine required for selectin-binding, is partially conserved in some fishes (e...
July 14, 2019: Journal of Leukocyte Biology
Rebecca Blandino, Nicole Baumgarth
Secreted IgM (sIgM) is a multifunctional evolutionary conserved antibody that is critical for the maintenance of tissue homeostasis as well as the development of fully protective humoral responses to pathogens. Constitutive secretion of self- and polyreactive natural IgM, produced mainly by B-1 cells, provides a circulating antibody that engages with autoantigens as well as invading pathogens, removing apoptotic and other cell debris and initiating strong immune responses. Pathogen-induced IgM production by B-1 and conventional B-2 cells strengthens this early, passive layer of IgM-mediated immune defense and regulates subsequent IgG production...
July 14, 2019: Journal of Leukocyte Biology
Vivian Cristina de Oliveira, Marcelo Pitombeira de Lacerda, Bárbara Bomfim Muniz Moraes, Caio Perez Gomes, Juliana Terzi Maricato, Olivia Fonseca Souza, Sergio Schenkman, João Bosco Pesquero, Nilmar Silvio Moretti, Celso Arrais Rodrigues, Ana Flavia Popi
Chronic lymphocytic leukemia (CLL) is a chronic form of leukemia that originates from an abnormal expansion of CD5+ B-1 cells. Deregulation in the BCR signaling is associated with B-cell transformation. Contrariwise to B-2 cells, BCR engagement in B-1 cells results in low proliferation rate and increased apoptosis population, whereas overactivation may be associated with lymphoproliferative disorders. It has been demonstrated that several transcription factors that are involved in the B cell development play a role in the regulation of BCR function...
July 12, 2019: Journal of Leukocyte Biology
Hiroyuki Ogasawara, Masahiro Furuno, Koji Edamura, Masato Noguchi
Human MCs are primary effectors implicated in immune surveillance and defense by secreting histamine and various inflammatory mediators, a mechanism termed as degranulation. MCs can be activated by two pathways: IgE-dependent classical pathway and the IgE-independent pathway that utilizes various cationic molecules including substance P (SP) and pituitary adenylate cyclase-activating polypeptides, which are host defense peptides collectively known as basic secretagogues. Our pharmacological study investigated whether or not IgE-independent MC activation is mediated via MRGPRX2...
July 12, 2019: Journal of Leukocyte Biology
Raquel Cavalcanti De Albuquerque, Alessandra Granato, Isabela Silva Castro, Rafael Carvalho Torres, Flávia Santos Souza, Marco Antonio Lima, Ana Claudia Celestino Bezerra Leite, Otávio de Melo Espíndola, Juliana Echevarria-Lima
Human T-cell lymphotropic virus type-1 (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic inflammatory disease that leads to gradual loss of motor movement as a result of the death of spinal cord cells through immune mediated mechanisms. The risk to develop HAM/TSP disease positively correlates with the magnitude of HTLV-1 proviral load. Gamma-delta T lymphocytes have been recognized as important players in a variety of infectious diseases...
July 9, 2019: Journal of Leukocyte Biology
Fauziyya Y Muhammad, Kayleigh Peters, Dawei Wang, Darren J Lee
Autoimmune uveitis is a leading cause of blindness with a complex etiology. Obesity is considered a chronic disease with a connection with autoimmune diseases through systemic inflammation. However, an obesity and autoimmune disease connection is not consistently true in rodent models of autoimmune disease. A mouse model of human autoimmune uveitis, experimental autoimmune uveitis (EAU) has been used to better understand the immunobiology of uveitis. In this study, we assessed EAU in a high-fat diet (HFD) obesity model and found that the EAU severity is significantly higher in wild-type mice, but not in HFD melanocortin 5 receptor deficient mice...
July 9, 2019: Journal of Leukocyte Biology
Daniel I Petkov, David X Liu, Carolina Allers, Peter J Didier, Elizabeth S Didier, Marcelo J Kuroda
Rhesus macaques are physiologically similar to humans and, thus, have served as useful animal models of human diseases including cardiovascular disease. The purpose of this study was to characterize the distribution, composition, and phenotype of macrophages in heart tissues of very young (fetus: 0.5 years, n = 6), young adult (2-12 years, n = 12), and older adult (13-24 years, n = 9) rhesus macaques using histopathology and immunofluorescence microscopy. Results demonstrated that macrophages were uniformly distributed throughout the heart in animals of all age groups and were more prevalent than CD3-positve T-cells and CD20-positive B-cells...
July 9, 2019: Journal of Leukocyte Biology
Hina N Khan, Desiree Perlee, Lieke Schoenmaker, Anne-Jan van der Meer, Marek Franitza, Mohammad Reza Toliat, Peter Nürnberg, Aeilko H Zwinderman, Tom van der Poll, Brendon P Scicluna
The host immune response is characterized by a complex interplay of signal-specific cellular transcriptional responses. The magnitude of the immune response is dependent on the strength of the external stimulus. Knowledge on leukocyte transcriptional responses altered in response to different stimulus dosages in man is lacking. Here, we sought to identify leukocyte transcriptional signatures dependent on LPS dose in humans. Healthy human volunteers were administered 1 ng/kg (n = 7), 2 ng/kg (n = 6), or 4 ng/kg (n = 7) LPS intravenously...
July 7, 2019: Journal of Leukocyte Biology
Karin E Bornfeldt
Discussion on the role of acyl-CoA synthetase 1 in immunometabolism.
July 3, 2019: Journal of Leukocyte Biology
Anne Lippitsch, Nelli Baal, Yuri Chukovetskyi, Sarah Cunningham, Gabriela Michel, Kristina Dietert, Corinne Gurtner, Achim D Gruber, Gregor Bein, Holger Hackstein
Plasmacytoid dendritic cells (pDC) are critical to antiviral defense because of their high production of type I IFNs; less is known regarding their functions in bacterial infection. Moreover, pDC are involved in immunomodulation. A stable pool of regulatory T cells (Treg) is crucial for maintaining immune homeostasis. However, interactions between pDC and Treg regarding the regulation of Treg homeostasis are understudied. By using BDCA2-DTR mice as a systemic pDC depletion model, we identified increased steady-state numbers of FoxP3+ T cells with an effector Treg-like phenotype in lungs, liver, and spleen tissues...
July 2, 2019: Journal of Leukocyte Biology
Adam J Fike, Ogan K Kumova, Alison J Carey
The neonatal period presents a complex scenario where the threshold of reactivity toward colonizing microbiota, maternal antigens, autoantigens, and pathogens must be carefully moderated and balanced. CD8+ T cells are critical for the response against intracellular bacteria and viruses, but this immune compartment maintains altered function relative to adult counterparts because of the unique challenges which infants face. Here, we review our current understanding of the factors which may promote the attenuation and altered function of the neonatal CD8+ T-cell response and potential avenues for future study...
July 1, 2019: Journal of Leukocyte Biology
Jun-Qi Yang, Khalid W Kalim, Yuan Li, Yi Zheng, Fukun Guo
Asthma is a heterogeneous chronic airway inflammation in which Th2 and Th17 cells are key players in its pathogenesis. We have reported that RhoA of Rho GTPases orchestrated glycolysis for Th2 cell differentiation and allergic airway inflammation by the use of a conditional RhoA-deficient mouse line. However, the role of RhoA in Th17 cells remains to be elucidated. In this study, we investigated the effects of RhoA deficiency on Th17 cells in the context of ex vivo cell culture systems and an in vivo house dust mites (HDM)-induced allergic airway inflammation...
July 1, 2019: Journal of Leukocyte Biology
Flávia Rago, Eliza Mathias Melo, Lucas Kraemer, Izabela Galvão, Geovanni D Cassali, Robson A S Santos, Remo C Russo, Mauro Martins Teixeira
Idiopathic pulmonary fibrosis is characterized by aberrant fibroblast activation and excessive collagen deposition that may eventually lead to organ dysfunction. Lung fibrosis is frequently observed in cancer patients undergoing bleomycin (BLM) treatment. Therefore, BLM instillation in mice is the most frequent model used to investigate pulmonary fibrosis. Angiotensin 1-7 [Ang-(1-7)] is a heptapeptide with anti-inflammatory and proresolving activity. Here, we studied the effects of preventive and therapeutic oral administration of Ang-(1-7) in a model of BLM-induced lung fibrosis in mice...
June 30, 2019: Journal of Leukocyte Biology
Kehong Zhang, Xin Wang, Jie Tu, Han Rong, Oliver Werz, Xinchun Chen
Depression is a major mental health condition and is expected be the most debilitating and widespread health disorder by 2030. Tuberculosis (TB) is also a leading cause of morbidity and mortality worldwide and interestingly, is a common comorbidity of depression. As such, much attention has been paid to the association between these 2 pathologies. Based on clinical reports, the association between TB and depression seems to be bidirectional, with a substantial overlap in symptoms between the 2 conditions. TB infection or reactivation may precipitate depression, likely as a consequence of the host's inflammatory response and/or dysregulation of the hypothalamic-pituitary-adrenal axis...
June 28, 2019: Journal of Leukocyte Biology
Marlene Christina Nielsen, Morten Nørgaard Andersen, Nikolaj Rittig, Sidsel Rødgaard-Hansen, Henning Grønbaek, Søren Kragh Moestrup, Holger Jon Møller, Anders Etzerodt
The hemoglobin receptor CD163 and the mannose receptor CD206 are both expressed on the surface of human macrophages. Upon inflammatory activation, the receptors are shed from the macrophage surface generating soluble products. The plasma concentration of both soluble CD163 (sCD163) and soluble CD206 (sCD206) are increased in several diseases, including inflammatory conditions and cancer. Here, we show that in contrast to CD163, LPS-mediated shedding of CD206 in humans is slow and a result of indirect signaling...
June 26, 2019: Journal of Leukocyte Biology
Theresa Ramalho, Latha Ramalingam, Luciano Filgueiras, William Festuccia, Sonia Jancar, Naima Moustaid-Moussa
Serum levels of leukotriene-B4 (LTB4) are increased in type 1 diabetes (T1D) and it mediates systemic inflammation and macrophage reprogramming associated with this condition. Herein, we investigated the involvement of LTB4 in adiposity loss, hyperlipidemia, and changes in macrophage metabolism in a mouse model of streptozotocin-induced T1D. LTB4 receptor (BLT1) antagonist u75302 was employed to block LTB4 effects. As expected, hypoinsulinemia in T1D was associated with hyperglycemia, low levels of glucagon, hyperlipidemia, significant body fat loss, and increased white adipose tissue expression of Fgf21, a marker for lipolysis...
June 26, 2019: Journal of Leukocyte Biology
Kensuke Miyake, Shin-Ichiroh Saitoh, Ryota Sato, Takuma Shibata, Ryutaro Fukui, Yusuke Murakami
TLRs respond to a variety of microbial products and initiate defense responses against bacteria and viruses. A variety of pathogens invade into and control the endosomal compartment to survive in host cells. On the other hand, host cells deploy cell surface and endosomal TLRs to pathogen-containing vesicles to mount defense responses. The endosomal compartment is a site for pathogen-sensing. As TLR-dependent defense responses are accompanied with a shift to the anabolic state, TLR responses need to be under metabolic control...
June 20, 2019: Journal of Leukocyte Biology
Michael H Lee, Paul M Gallo, Kirsten M Hooper, Chelsea Corradetti, Doina Ganea, Roberto Caricchio, Stefania Gallucci
IL-10 is elevated in the autoimmune disease systemic lupus erythematosus (SLE). Here, we show that conventional dendritic cells (cDCs) from predisease lupus-prone B6.NZM Sle1/Sle2/Sle3 triple congenic (TCSle) mice produce more IL-10 than wild-type congenic cDCs upon TLR stimulation, and this overproduction is prevented by blocking the type I IFN receptor (IFNAR) with specific Abs. Priming wild-type cDCs with type I IFN mimics the IL-10 overproduction of TCSle cDCs. The MAPK ERK is more phosphorylated in lupus cDCs, partially contributing to IL-10 overproduction...
June 19, 2019: Journal of Leukocyte Biology
Stephanie Saul, Cyril Castelbou, Céline Fickentscher, Nicolas Demaurex
Neutrophils play a central role in immunity and inflammation via their intrinsic ability to migrate into inflamed tissue, to phagocytose pathogens, and to kill bacterial and fungi by releasing large quantities of superoxide anions and lytic enzymes. The molecular pathways controlling neutrophil microbicidal functions are still unclear, because neutrophils have a short half-life and are resistant to genetic manipulation. Neutrophil-like cells (NLC) can be generated from myeloid progenitors conditionally immortalized with the ER-HoxB8 oncoprotein, but whether these cells can replace neutrophils in high-throughput functional assays is unclear...
June 19, 2019: Journal of Leukocyte Biology
Li Hao, Xi Lei, Hong Zhou, Aaron J Marshall, Lixin Liu
PI3K has been indicated in regulating microvascular permeability changes during inflammation. However, its role in neutrophil-driven microvascular leakage in acute inflammation remains unclear. Using intravital microscopy in mice, we examined the role of PI3Kγ and PI3Kδ in formyl peptide WKYMVm- and chemokine CXCL2-induced permeability changes and assessed simultaneously neutrophil adhesion and emigration in post-capillary venules of murine cremaster muscle. We found a PI3Kγ-specific mechanism in WKYMVm-induced but not CXCL2-induced microvascular hyperpermeability...
June 19, 2019: Journal of Leukocyte Biology
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