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Complement receptor 3

Lin Li, Xiaotian Qi, Weili Sun, Hisham Abdel-Azim, Siyue Lou, Hong Zhu, Nemani V Prasadarao, Alice Zhou, Hiroyuki Shimada, Koichi Shudo, Yong-Mi Kim, Sajad Khazal, Qiaojun He, David Warburton, Lingtao Wu
Neutrophils generated by granulocyte colony-stimulating factor (GCSF) are functionally immature and, consequently, cannot effectively reduce infection and infection-related mortality in cancer chemotherapy-induced neutropenia (CCIN). Am80, a retinoic acid (RA) agonist that enhances granulocytic differentiation by selectively activating transcription factor RA receptor alpha (RARα), alternatively promotes RA-target gene expression. We found that in normal and malignant primary human hematopoietic specimens, Am80-GCSF combination coordinated proliferation with differentiation to develop complement receptor-3 (CR3)-dependent neutrophil innate immunity, through altering transcription of RA-target genes RARβ2, C/EBPε, CD66, CD11b, and CD18 This led to generation of functional neutrophils capable of fighting infection, whereas neutralizing neutrophil innate immunity with anti-CD18 antibody abolished neutrophil bactericidal activities induced by Am80-GCSF Further, Am80-GCSF synergy was evaluated using six different dose-schedule-infection mouse CCIN models...
October 13, 2016: EMBO Molecular Medicine
Aihua Hou, Kai Pong Law, Min Qi Tin, Yoon Pin Lim, Louis Tong
Pterygium is a triangular shaped ocular fibrous surface lesion growing from conjunctiva towards central cornea, causing ocular irritation, astigmatism, and visual disturbance. The condition is characterized by epithelial proliferation, fibrovascular growth, chronic inflammation, and prominent extracellular matrix remodeling. Studies have suggested that aberrant extracellular proteins secreted by fibroblasts lead to abnormal matrix production and tissue invasion contributing to the development of the disease...
October 7, 2016: Experimental Eye Research
Kenta Fujimoto, Takehiro Motowaki, Naoya Tamura, Yasuaki Aratani
Myeloperoxidase (MPO), a major component of neutrophils, catalyzes the production of hypochlorous acid from hydrogen peroxide and chloride anion. Phagocytosis is a critical event induced by neutrophils for host defense and inflammation. Interestingly, we found that MPO-deficient (MPO(-/-)) neutrophils engulfed larger amounts of zymosan than wild-type neutrophils. Blocking of the CD11b subunit of complement receptor 3 (CR3) as well as inhibition of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) dramatically reduced zymosan phagocytosis...
October 4, 2016: Free Radical Research
Xian M O'Brien, Jonathan S Reichner
Neutrophils are motile and responsive to tissue injury and infection. As neutrophils emigrate from the bloodstream and migrate toward a site of affliction, they encounter the tissue extracellular matrix (ECM) and thereby engage integrins. Our laboratory studies the neutrophilic response to the fungal pathogen Candida albicans either in the filamentous state of the microbe or to the purified pathogen-associated molecular pattern, β-glucan. We have gained an appreciation for the role of integrins in regulating the neutrophil anti-Candida response and how the presence or absence of ECM can drive experimental outcome...
2016: Frontiers in Immunology
Pei Wu, Wei-Dan Jiang, Jun Jiang, Juan Zhao, Yang Liu, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
This study investigated the effects of choline on intestinal mucosal immune and the possible mechanisms in fish by feeding juvenile Jian carp (Cyprinus carpio var. Jian) with graded levels of dietary choline (165-1820 mg/kg diet) for 65 days. The results firstly showed that choline deficiency induced inflammatory infiltration in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) of fish. Meanwhile, compared with the optimal choline group, choline deficiency decreased the activities of lysozyme and acid phosphatase, contents of complement 3 and IgM in the intestine, downregulated the mRNA levels of antimicrobial peptides (liver-expressed antimicrobial peptide (LEAP) 2A and defensin-3 in the PI and MI, LEAP-2B and hepcidin in the PI, MI and DI), anti-inflammatory cytokines (interleukin (IL) 10 and transforming growth factor β2 in the PI, MI and DI), and signaling molecule IκB in the PI, MI and DI; while upregulated the mRNA levels of pro-inflammatory cytokines (IL-6a and tumor necrosis factor α in the MI and DI, interferon γ2b in the PI and MI, IL-1β and IL-6b in the PI, MI and DI), and signaling molecules (Toll-like receptor 4 in the MI, myeloid differentiation primary response 88 in the PI and MI, Janus kinase 3 and tyrosine kinase 2 in the MI and DI, nuclear factor kappa B (NF-κB), signal transducers and activators of transcription (STAT) 4 and STAT5 in the PI, MI and DI) of juvenile Jian carp, further indicating that choline deficiency caused inflammation and immunity depression in the intestine of fish...
September 28, 2016: Fish & Shellfish Immunology
C Damgaard, J Reinholdt, Y Palarasah, C Enevold, C Nielsen, M K Brimnes, P Holmstrup, C H Nielsen
BACKGROUND AND OBJECTIVE: The periodontal pathogen Aggregatibacter actinomycetemcomitans has been proposed as pro-atherogenic, and complement-mediated adherence to red blood cells (RBCs) may facilitate its systemic spread. We investigated the ability of four strains of A. actinomycetemcomitans with differential expression of leukotoxin A (LtxA) and fimbriae to activate complement, adhere to RBCs and elicit cytokine responses by mononuclear cells (MNCs). MATERIAL AND METHODS: Aggregatibacter actinomycetemcomitans serotype b strains HK 921, HK 1651, HK 2092 and HK 2108 were fluorescence-labeled, incubated with human whole blood cells in the presence of autologous serum, and assessed for RBC adherence by flow cytometry and for capacity to induce cytokine production by cytometric bead array analysis...
September 24, 2016: Journal of Periodontal Research
Serban Radian, Yoan Diekmann, Plamena Gabrovska, Brendan Holland, Lisa Bradley, Helen Wallace, Karen Stals, Anna-Marie Bussell, Karen McGurren, Martin Cuesta, Anthony W Ryan, Maria Herincs, Laura C Hernández-Ramírez, Aidan Holland, Jade Samuels, Elena Daniela Aflorei, Sayka Barry, Judit Dénes, Ida Pernicova, Craig E Stiles, Giampaolo Trivellin, Ronan McCloskey, Michal Ajzensztejn, Noina Abid, Scott A Akker, Moises Mercado, Mark Cohen, Rajesh V Thakker, Stephanie Baldeweg, Ariel Barkan, Madalina Musat, Miles Levy, Stephen M Orme, Martina Unterländer, Joachim Burger, Ajith V Kumar, Sian Ellard, Joseph McPartlin, Ross McManus, Gerard J Linden, Brew Atkinson, David J Balding, Amar Agha, Chris J Thompson, Steven J Hunter, Mark G Thomas, Patrick J Morrison, Márta Korbonits
The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304(*) (or p.R304(*) ; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304(*) carrier frequency in 936 Mid Ulster, 1,000 Greater Belfast (both in NI) and 2,094 Republic of Ireland (ROI) volunteers and in 116 NI or ROI acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027-0...
September 21, 2016: Human Mutation
Judit Tenk, Ildikó Rostás, Nóra Füredi, Alexandra Mikó, Szilvia Soós, Margit Solymár, Balázs Gaszner, Miklós Székely, Erika Pétervári, Márta Balaskó
Previously demonstrated age-related changes in the catabolic melanocortin system that may contribute to middle-aged obesity and aging anorexia, raise the question of the potential involvement of corticotropin-releasing factor (CRF) in these phenomena, as this catabolic hypothalamic mediator acts downstream to melanocortins. Catabolic effects of CRF were shown to be mediated by both CRF1 (hypermetabolism) and CRF2 (anorexia) receptors. To test the potential role of CRF in age-related obesity and aging anorexia, we investigated acute central effects of the peptide on energy balance in male and female rats during the course of aging...
September 13, 2016: Peptides
Jiehong Zhao, Jie Han, Jie Zhang, Zhenhua Li, Jing Yu, Shizhou Yu, Yushuang Guo, Yongfu Fu, Xiaomei Zhang
Polyphenols are important secondary metabolites and bioactive compounds in plants. Light is a vital abiotic factor that greatly impacts the content of polyphenols in plants. In spite of their importance the mechanism of polyphenol regulation still remains unknown in tobacco. A phytochrome B homolog, NtPHYB1(K326), was isolated from Nicotiana tabacum cv. K326 to investigate the role of light receptors in the regulation of polyphenol metabolism in tobacco leaves. Furthermore, role of NtPHYB1(K326) in polyphenol metabolism was analyzed by over-expression and RNAi-silencing approaches...
August 31, 2016: Plant Physiology and Biochemistry: PPB
Sandra Rother, Sergey A Samsonov, Ute Hempel, Sarah Vogel, Stephanie Moeller, Joanna Blaszkiewicz, Sebastian Köhling, Matthias Schnabelrauch, Jörg Rademann, M Teresa Pisabarro, Vera Hintze, Dieter Scharnweber
Sulfated glycosaminoglycans (sGAGs) modulate cellular processes via their interaction with extracellular matrix (ECM) proteins. We revealed a direct binding of tissue inhibitor of metalloproteinase-3 (TIMP-3) to the endocytic receptor low-density lipoprotein receptor-related protein (LRP-1) clusters II and IV using surface plasmon resonance. Sulfated hyaluronan (sHA) and chondroitin sulfate (sCS) derivatives interfered with TIMP-3/LRP-1 complex formation in a sulfation-dependent manner stronger than heparin...
October 10, 2016: Biomacromolecules
Ling Zhu, Xiangxi Wang, Jingshan Ren, Abhay Kotecha, Thomas S Walter, Shuai Yuan, Teruo Yamashita, Tobias J Tuthill, Elizabeth E Fry, Zihe Rao, David I Stuart
Aichi virus (AiV), an unusual and poorly characterized picornavirus, classified in the genus Kobuvirus, can cause severe gastroenteritis and deaths in children below the age of five years, especially in developing countries(1,2). The seroprevalence of AiV is approximately 60% in children under the age of ten years and reaches 90% later in life(3,4). There is no available vaccine or effective antiviral treatment. Here, we describe the structure of AiV at 3.7 Å. This first high-resolution structure for a kobuvirus is intermediate between those of the enteroviruses and cardioviruses, with a shallow, narrow depression bounded by the prominent VP0 CD loops (linking the C and D strands of the β-barrel), replacing the depression known as the canyon, frequently the site of receptor attachment in enteroviruses...
2016: Nature Microbiology
Sumitaka Kobayashi, Fumihiro Sata, Seiko Sasaki, Titilola Serifat Braimoh, Atsuko Araki, Chihiro Miyashita, Houman Goudarzi, Sachiko Kobayashi, Reiko Kishi
OBJECTIVES: We investigated the individual and combined effects of maternal polymorphisms encoding the aromatic hydrocarbon receptor (AHR; rs2066853), cytochrome P450 (CYP) 1A1 (rs1048963), and the X-ray-complementing gene 1 (XRCC1; rs1799782) and prenatal smoking in relation to infant birth size. METHODS: Totally, 3263 participants (1998 non-smokers and 1265 smokers) were included in the study between 2003 and 2007. Two groups of mothers were distinguished by plasma cotinine levels by ELISA measured during the third trimester (cut-off=11...
October 2016: Reproductive Toxicology
Jayanth Suryanarayanan Shankaranarayanan, Jagat R Kanwar, Afrah Jalil Abd Al-Juhaishi, Rupinder K Kanwar
Advanced, metastatic, castration resistant and chemo-resistant prostate cancer has triggered change in the drug development landscape against prostate cancer. Bovine lactoferrin (bLf) is currently attracting attention in clinics for its anti-cancer properties and proven safety profile. bLf internalises into cancer cells via receptor mediated endocytosis, boosts immunity and complements chemotherapy. We employed bLf as an excellent functional carrier protein for delivering doxorubicin (Dox) into DU145 cells, CD44+/EpCAM+ double positive enriched DU145 3D prostaspheres and drug resistant ADR1000-DU145 cells, thus circumventing Dox efflux, to overcome chemo-resistance...
2016: Scientific Reports
Mark F McCarty, James DiNicolantonio
Lysophosphatidic acid (LPA), generated in the microenvironment of cancer cells, can drive the proliferation, invasion, and migration of cancer cells by activating G protein-coupled LPA receptors. Moreover, in cancer cells that have metastasized to bone, LPA signaling can promote osteolysis by inducing cancer cell production of cytokines, such as IL-6 and IL-8, which can stimulate osteoblasts to secrete RANKL, a key promoter of osteoclastogenesis. Indeed, in cancers prone to metastasize to bone, LPA appears to be a major driver of the expansion of osteolytic bone metastases...
August 25, 2016: Healthcare (Basel, Switzerland)
John Baer, Isaiah Taylor, John C Walker
In Arabidopsis thaliana, the process of abscission, or the shedding of unwanted organs, is mediated by two genes, HAESA (HAE) and HAESA-LIKE 2 (HSL2), encoding receptor-like protein kinases (RLKs). The double loss-of-function mutant hae-3 hsl2-3 is completely deficient in floral abscission, but, interestingly, the hae-3 hsl2-9 mutant displays a less severe defect. This mutant was chosen for an ethyl methanesulfonate (EMS) screen to isolate enhancer and suppressor mutants, and two such suppressors are the focus of this study...
October 2016: Journal of Experimental Botany
Beate Hintersteiner, Nico Lingg, Peiqing Zhang, Susanto Woen, Kong Meng Hoi, Stefan Stranner, Susanne Wiederkum, Oliver Mutschlechner, Manfred Schuster, Hans Loibner, Alois Jungbauer
We identified active isoforms of the chimeric anti-GD2 antibody, ch14.18, a recombinant antibody produced in Chinese hamster ovary cells, which is already used in clinical trials. (1,2,3) We separated the antibody by high resolution ion-exchange chromatography with linear pH gradient elution into acidic, main and basic charge variants on a preparative scale yielding enough material for an in-depth study of the sources and the effects of microheterogeneity. The binding affinity of the charge variants toward the antigen and various cell surface receptors was studied by Biacore...
August 25, 2016: MAbs
Anne Müller, Lars Niederstadt, Wenke Jonas, Chun-Xia Yi, Franziska Meyer, Petra Wiedmer, Jana Fischer, Carsten Grötzinger, Annette Schürmann, Matthias Tschöp, Gunnar Kleinau, Annette Grüters, Heiko Krude, Heike Biebermann
Intact melanocortin signaling via the G protein-coupled receptors (GPCRs), melanocortin receptor 4 (MC4R), and melanocortin receptor 3 (MC3R) is crucial for body weight maintenance. So far, no connection between melanocortin signaling and hypothalamic inflammation has been reported. Using a bimolecular fluorescence complementation library screen, we identified a new interaction partner for these receptors, ring finger protein 11 (RNF11). RNF11 participates in the constitution of the A20 complex that is involved in reduction of tumor necrosis factor α (TNFα)-induced NFκB signaling, an important pathway in hypothalamic inflammation...
2016: Frontiers in Endocrinology
Ainhoa Arbués, Wladimir Malaga, Patricia Constant, Christophe Guilhot, Jacques Prandi, Catherine Astarie-Dequeker
Despite mycobacterial pathogens continue to be a threat to public health, the mechanisms that allow them to persist by modulating the host immune response are poorly understood. Among the factors suspected to play a role are phenolic glycolipids (PGLs), produced notably by the major pathogenic species such as Mycobacterium tuberculosis and Mycobacterium leprae. Here, we report an original strategy combining genetic reprogramming of the PGL pathway in Mycobacterium bovis BCG and chemical synthesis to examine whether sugar variations in the species-specific PGLs have an impact on pattern recognition receptors (PRRs) and the overall response of infected cells...
October 21, 2016: ACS Chemical Biology
Christian Machacek, Verena Supper, Vladimir Leksa, Goran Mitulovic, Andreas Spittler, Karel Drbal, Miloslav Suchanek, Anna Ohradanova-Repic, Hannes Stockinger
Folate, also known as vitamin B9, is necessary for essential cellular functions such as DNA synthesis, repair, and methylation. It is supplied to the cell via several transporters and receptors, including folate receptor (FR) β, a GPI-anchored protein belonging to the folate receptor family. As FRβ shows a restricted expression to cells of myeloid origin and only a subset of activated macrophages and placental cells have been shown to express functional FRβ, it represents a promising target for future therapeutic strategies...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Daniel M Houslay, Karen E Anderson, Tamara Chessa, Suhasini Kulkarni, Ralph Fritsch, Julian Downward, Jonathan M Backer, Len R Stephens, Phillip T Hawkins
Class I phosphoinositide 3-kinases (PI3Ks) catalyze production of the lipid messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3), which plays a central role in a complex signaling network regulating cell growth, survival, and movement. This network is overactivated in cancer and inflammation, and there is interest in determining the PI3K catalytic subunit (p110α, p110β, p110γ, or p110δ) that should be targeted in different therapeutic contexts. Previous studies have defined unique regulatory inputs for p110β, including direct interaction with Gβγ subunits, Rac, and Rab5...
2016: Science Signaling
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