DOCSLIB.ORG

A Novel Α9 Integrin Ligand, XCL1/Lymphotactin, Is Involved in the Development of Murine Models of Autoimmune Diseases

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Novel Α9 Integrin Ligand, XCL1/Lymphotactin, Is Involved in the Development of Murine Models of Autoimmune Diseases A Novel α9 Integrin Ligand, XCL1/Lymphotactin, Is Involved in the Development of Murine Models of Autoimmune Diseases This information is current as of September 25, 2021. Naoki Matsumoto, Shigeyuki Kon, Takuya Nakatsuru, Tomoe Miyashita, Kyosuke Inui, Kodai Saitoh, Yuichi Kitai, Ryuta Muromoto, Jun-ichi Kashiwakura, Toshimitsu Uede and Tadashi Matsuda J Immunol 2017; 199:82-90; Prepublished online 26 May Downloaded from 2017; doi: 10.4049/jimmunol.1601329 http://www.jimmunol.org/content/199/1/82 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2017/05/26/jimmunol.160132 Material 9.DCSupplemental References This article cites 40 articles, 20 of which you can access for free at: http://www.jimmunol.org/content/199/1/82.full#ref-list-1 by guest on September 25, 2021 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2017 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology A Novel a9 Integrin Ligand, XCL1/Lymphotactin, Is Involved in the Development of Murine Models of Autoimmune Diseases Naoki Matsumoto,*,1 Shigeyuki Kon,*,†,1 Takuya Nakatsuru,* Tomoe Miyashita,* Kyosuke Inui,* Kodai Saitoh,* Yuichi Kitai,* Ryuta Muromoto,* Jun-ichi Kashiwakura,* Toshimitsu Uede,‡ and Tadashi Matsuda* The integrin a9b1 is a key receptor involved in the development of autoimmune diseases. However, the detailed mechanism for the association of a9b1 integrin with its ligands remains unclear. In this study, we introduce XCL1/lymphotactin, a member of the chemokine family, as a novel ligand for a9 integrin. Using a9 integrin–overexpressing NIH3T3 cells and endogenously a9 integrin–expressing human rhabdomyosarcoma cells, the interaction between XCL1 and a9 integrin was confirmed by pull- Downloaded from down assays. XCL1 enhanced a9 integrin–dependent cell migration of these cells, thus acting on a9 integrin as a chemoattractant. We also analyzed the in vivo function of XCL1 in the development of anti-type II collagen Ab–induced inflammatory arthritis (CAIA) in BALB/c mice and experimental autoimmune encephalomyelitis in C57BL/6 mice, because a9 integrin is involved in these autoimmune disease models. In CAIA, recombinant XCL1 aggravated the disease and this exacerbation was inhibited by an anti-a9 integrin Ab. An XCL1-neutralizing Ab produced in this study also ameliorated CAIA. Furthermore, the XCL1- neutralizing Ab abrogated the disease progression in experimental autoimmune encephalomyelitis. Therefore, to our knowledge http://www.jimmunol.org/ this study provides the first in vitro and in vivo evidence that the interaction between XCL1 and a9 integrin has an important role for autoimmune diseases. The Journal of Immunology, 2017, 199: 82–90. ntegrins are transmembrane receptors involved in a wide cephalomyelitis (EAE) (11). However, inhibition or knockout of OPN range of cellular processes, including cell adhesion, migra- has lesser effects than the use of the anti-a9 integrin Ab (12–14), and I tion, differentiation, proliferation, and apoptosis, and cancer the involvement of other a9 integrin ligands in CAIA remains un- metastasis (1–5). a9 integrin binds to various extracellular matrix known, indicating that there may be other players in the development proteins, including osteopontin (OPN), tenascin-C (TN-C), and vas- of autoimmune diseases. Therefore, we searched for a candidate a9 by guest on September 25, 2021 cular endothelial growth factor C and D, and is associated with integrin ligand by liquid chromatography tandem-mass spectrometry autoimmune diseases such as arthritis (6–9). An anti-a9 integrin– (LC-MS/MS) analysis and identified XCL1/lymphotactin. blocking Ab was reported to ameliorate the disease scores in collagen In this study, we demonstrate that XCL1 functions in autoim- Ab–induced arthritis (CAIA) (10) and experimental autoimmune en- mune diseases as a novel a9 integrin ligand. A physiological interaction between a9 integrin and XCL1 was confirmed by pull- down assays. XCL1 belongs to the C-class of chemokines, and its *Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido Uni- only known receptor is XCR1 (15). We found that XCL1 stimu- versity, Sapporo 060-0815, Japan; †Department of Molecular Immunology, Faculty of lation enhanced cell migration in a9 integrin–expressing cells, and Pharmaceutical Sciences, Fukuyama University, Fukuyama 729-0292, Japan; and ‡Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido Uni- that this XCL1-dependent cell migration was suppressed by a versity, Sapporo 060-0817, Japan function-blocking anti-a9 integrin Ab. To further investigate the 1N.M. and S.K. contributed equally to this work. role of XCL1 in vivo, we generated an XCL1-neutralizing mAb, ORCID: 0000-0001-5410-8429 (S.K.). 1A3A. The 1A3A Ab successfully protected mice against CAIA, Received for publication August 3, 2016. Accepted for publication April 27, 2017. indicating that XCL1 is involved in the development of this dis- This work was supported in part by Japan Society for the Promotion of Science ease. We also administered the Ab to mice with EAE, and ob- KAKENHI Grants JP24590072 and JP16K08221, the Fugaku Trust for Medical served amelioration of the disease. Recently, XCL1 expression Research, the Research Foundation for Pharmaceutical Sciences, The Nakatomi was demonstrated to be elevated in patients with rheumatoid ar- Foundation, the Japan Rheumatism Foundation, Pfeizer Academic Contributions, and the Pharmacological Research Foundation. thritis (RA) (16), whereas a9 integrin expression was reported to Address correspondence and reprint requests to Prof. Shigeyuki Kon, Department of be increased in the RA synovium (9). Taken together, it is sug- Molecular Immunology, Faculty of Pharmaceutical Sciences, Fukuyama University, gested that the interaction between XCL1 and a9 integrin can be a 985-1 Azasanzo, Higashimura-cho, Fukuyama, Hiroshima 729-0292, Japan. E-mail new therapeutic target for autoimmune diseases. address: [email protected] The online version of this article contains supplemental material. Materials and Methods Abbreviations used in this article: CAIA, collagen Ab–induced arthritis; CHO, Chinese hamster ovary; EAE, experimental autoimmune encephalomyelitis; FLS, Cell culture and reagents fibroblast-like synoviocyte; HPRT, hypoxanthine-guanine phosphoribosyltransfer- NIH3T3 cells, Chinese hamster ovary (CHO) cells, HEK293T cells, Plat-GP ase; Kir, inward-rectifier potassium; LC-MS/MS, liquid chromatography tandem- mass spectrometry; MOG, myelin oligodendrocyte glycoprotein; OPN, osteopontin; cells, rhabdomyosarcoma (RD) cells (derived from a human rhabdomyo- qPCR, quantitative PCR; RA, rheumatoid arthritis; RD, rhabdomyosarcoma; TN-C, sarcoma), and fibroblast-like synoviocytes (FLS) were cultured in DMEM tenascin-C. containing 10% FBS (HyClone, Logan, UT). Ba/F3, an IL-3–dependent murine pro-B cell line, was maintained in RPMI 1640 medium supple- Copyright Ó 2017 by The American Association of Immunologists, Inc. 0022-1767/17/$30.00 mented with 10% FCS and 10% WEHI-3B conditioned medium as a www.jimmunol.org/cgi/doi/10.4049/jimmunol.1601329 The Journal of Immunology 83 source of IL-3. HRP-conjugated anti-human IgG (Jackson Immuno- generation of various His-SUMO-tagged mouse XCL1 variants, the target Research, West Grove, PA) was used for ELISA and Western blot analysis. genes were PCR amplified using the following primers: 59-TATTGAGGCT- Anti-rat IgG (Jackson ImmunoResearch) was used for ELISA. Anti-His- CATCGCGAACAGATTGGAGGTGTGGGGACTGAAGTCCTA-39 (sense) tag Ab OGHis (MBL, Nagoya, Japan) and anti-FLAG-tag Ab 1E6 and 59-ATGCCTGCAGGTCGACTTACCCAGTCAGGGTTATCGCTG-39 (an- (WAKO, Osaka, Japan) were used for Western blot analyses. Anti-human tisense) for full, 59-TATTGAGGCTCATCGCGAACAGATTGGAGGTGTGG- a9 integrin mAb Y9A2 (Chemicon, Temecula, CA) was used for flow GGACTGAAGTCCTA-39 (sense) and 59-ATGCCTGCAGGTCGACTTAAG- cytometry and cell migration assays. An anti-a9 integrin polyclonal Ab for TCTTGATCGCTGCTTTCA-39 (antisense) for 22–83, 59-TATTGAGGCT- Western blot analyses was generated by immunizing a rabbit with a pep- CATCGCGAACAGATTGGAGGTGGGGCCATGAGAGCTGTA-39 (sense) tide derived from the C-terminal domain of human a9 integrin, and 59-ATGCCTGCAGGTCGACTTACCCAGTCAGGGTTATCGCTG-39 CEAEKNRKENEDSWDWVQKNQ. IgG from human serum (Sigma- (antisense) for 53–114, 59-TATTGAGGCTCATCGCGAACAGATTGGA- Aldrich, St. Louis, MO), and recombinant His-tagged human XCL1 pro- GGTATTTGTGCTGATCCAGAA-39 (sense) and 59-ATGCCTGCAG- tein (hXCL1-His) (PeproTech, Rocky Hill, NJ) were used for cell migra- GTCGACTTACCCAGTCAGGGTTATCGCTG-39 (antisense) for 68–114, tion assays. 59-TATTGAGGCTCATCGCGAACAGATTGGAGGTGTGGATGGCAGGG- CCAGT-39 (sense) and 59-ATGCCTGCAGGTCGACTTACCCAGTCAGG- Generation of stable cell lines GTTATCGCTG-39
Load more

Recommended publications
  • Supplementary Table 1: Adhesion Genes Data Set
    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
    [Show full text]
  • Rescuing Functional T Cells Induced by Growth Factor Deprivation, CCL2 Inhibits the Apoptosis Program
    CCL2 Inhibits the Apoptosis Program Induced by Growth Factor Deprivation, Rescuing Functional T Cells This information is current as Eva Diaz-Guerra, Rolando Vernal, M. Julieta del Prete, of September 24, 2021. Augusto Silva and Jose A. Garcia-Sanz J Immunol 2007; 179:7352-7357; ; doi: 10.4049/jimmunol.179.11.7352 http://www.jimmunol.org/content/179/11/7352 Downloaded from References This article cites 41 articles, 21 of which you can access for free at: http://www.jimmunol.org/content/179/11/7352.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 24, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2007 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology CCL2 Inhibits the Apoptosis Program Induced by Growth Factor Deprivation, Rescuing Functional T Cells1 Eva Diaz-Guerra,2 Rolando Vernal,2 M. Julieta del Prete,2 Augusto Silva, and Jose A. Garcia-Sanz3 The precise mechanisms involved in the switch between the clonal expansion and contraction phases of a CD8؉ T cell response remain to be fully elucidated.
    [Show full text]
  • Interleukin-15-Mediated Immunotoxicity and Exacerbation of Sepsis
    INTERLEUKIN-15-MEDIATED IMMUNOTOXICITY AND EXACERBATION OF SEPSIS: ROLE OF NATURAL KILLER CELLS AND INTERFERON γ By Yin Guo Dissertation Submitted to the Faculty of the Graduate School of Vanderbilt University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in Microbiology and Immunology December 2016 Nashville, Tennessee Approved Luc Van Kaer, Ph.D. Stokes Peebles, M.D. Lorraine Ware, M.D. Daniel Moore, M.D., Ph.D. Edward Sherwood, M.D, Ph.D. i Copyright © 2016 by Yin Guo All Rights Reserved ii ACKNOWLEDGEMENTS I would like to thank my thesis mentor, Dr. Edward Sherwood for his tremendous instruction and support during my entire Ph.D. training course. I joined Dr. Sherwood’s lab in the department of Microbiology and Immunology of University of Texas Medical Branch (UTMB) at Galveston in 2011. I appreciated the offer Dr. Sherwood provided to move to Vanderbilt University together. During the new lab setup period, he gave me a lot of encouragement about going out to meet students and professors at the Pathology, Microbiology and Immunology Department. From making new friends in our department, I started to know a lot of useful information and resources about how to adapt to new life in Nashville and how to prepare for the qualifying exam. Dr. Sherwood is a highly responsible and enthusiastic mentor although he has busy medical practice in the operating room and needs to write many grants. I have to say, he is the most diligent person I have seen in the world. It is amazing to me that he never seems to be exhausted or desensitized with reviewing our papers, reading papers, writing grants, and discussing data and new ideas.
    [Show full text]
  • Metamorphic Protein Folding Encodes Multiple Anti-Candida Mechanisms in XCL1
    pathogens Article Metamorphic Protein Folding Encodes Multiple Anti-Candida Mechanisms in XCL1 Acacia F. Dishman 1,2,†, Jie He 3,†, Brian F. Volkman 1,* and Anna R. Huppler 3,* 1 Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA; [email protected] 2 Medical Scientist Training Program, Medical College of Wisconsin, Milwaukee, WI 53226, USA 3 Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA; [email protected] * Correspondence: [email protected] (B.F.V.); [email protected] (A.R.H.) † These authors contributed equally. Abstract: Candida species cause serious infections requiring prolonged and sometimes toxic therapy. Antimicrobial proteins, such as chemokines, hold great interest as potential additions to the small number of available antifungal drugs. Metamorphic proteins reversibly switch between multiple different folded structures. XCL1 is a metamorphic, antimicrobial chemokine that interconverts between the conserved chemokine fold (an α–β monomer) and an alternate fold (an all-β dimer). Previous work has shown that human XCL1 kills C. albicans but has not assessed whether one or both XCL1 folds perform this activity. Here, we use structurally locked engineered XCL1 variants and Candida killing assays, adenylate kinase release assays, and propidium iodide uptake assays to demonstrate that both XCL1 folds kill Candida, but they do so via different mechanisms. Our results suggest that the alternate fold kills via membrane disruption, consistent with previous work, and the chemokine fold does not. XCL1 fold-switching thus provides a mechanism to regulate Citation: Dishman, A.F.; He, J.; the XCL1 mode of antifungal killing, which could protect surrounding tissue from damage associ- Volkman, B.F.; Huppler, A.R.
    [Show full text]
  • Lymphotactin Mediates Antiviral T Cell Trafficking Within
    LYMPHOTACTIN MEDIATES ANTIVIRAL T CELL TRAFFICKING WITHIN THE CENTRAL NERVOUS SYSTEM DURING WEST NILE VIRUS ENCEPHALITIS A Thesis Presented to the Faculty of California State Polytechnic University, Pomona In Partial Fulfillment Of the Requirements for the Degree Master of Science In Biological Sciences By Sharese Tronti 2019 SIGNATURE PAGE THESIS: LYMPHOTACTIN MEDIATES ANTIVIRAL T CELL TRAFFICKING WITHIN THE CENTRAL NERVOUS SYSTEM DURING WEST NILE VIRUS ENCEPHALITIS AUTHOR: Sharese Tronti DATE SUBMITTED: Spring 2019 Department of Biological Sciences Dr. Douglas Durrant Thesis Committee Chair Biological Sciences Dr. Andrew Steele Biological Sciences Dr. Jamie Snyder Biological Science ii ABSTRACT West Nile Virus (WNV), a neurotropic flavivirus, can cause neuroinvasive disease in humans. After peripheral infection, WNV is able to enter the central nervous system (CNS) and infect neurons causing neuronal injury and inflammation that potentially may result in fatality. In order to restrict viral replication and pathogenesis within the CNS during WNV encephalitis, virus-specific CD8+ T cells are critically dependent on dendritic cell (DC) mediated reactivation at this site. However, the mechanism by which DCs are recruited to the brain to ensure their interaction with infiltrating virus-specific CD8+ T cells remains unknown. Previous studies have demonstrated that, upon activation, CD8+ T cells rapidly produce the chemokine lymphotactin when activated. The receptor for lymphotactin, XCR1, is exclusively expressed on a subset of DCs, CD8+ DCs, which have been shown to be essential in establishing protective peripheral immunity against viruses and intracellular bacteria. In this study, we show that lymphotactin regulates the CNS entry of T lymphocytes, potentially promoting virologic control within the CNS and limiting neuronal cell death.
    [Show full text]
  • Anti-ITGA9 Monoclonal Antibody, Clone FQS0833 (DCABH-3776) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use
    Anti-ITGA9 monoclonal antibody, clone FQS0833 (DCABH-3776) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Product Overview Rabbit monoclonal to Integrin alpha 9 Antigen Description Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. Immunogen Synthetic peptide (the amino acid sequence is considered to be commercially sensitive) Isotype IgG Source/Host Rabbit Species Reactivity Mouse, Rat, Human Clone FQS0833 Purity Tissue culture supernatant Conjugate Unconjugated Applications WB, IHC-P Positive Control NIH3T3, A673, HepG2, and A549 cell lysates, Human lung and Human skin tissues Format Liquid Size 100 μl Buffer Preservative: 0.01% Sodium azide; Constituents: 50% Glycerol, 0.05% BSA Preservative 0.01% Sodium Azide Storage store at -20°C. Avoid freeze / thaw cycles. Ship Shipped at 4°C. GENE INFORMATION Gene Name ITGA9 integrin, alpha 9 [ Homo sapiens ] Official Symbol ITGA9 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 1 © Creative Diagnostics All Rights Reserved Synonyms ITGA9; integrin, alpha 9; integrin alpha-9; ALPHA RLC; integrin; alpha 4 like; ITGA4L; RLC; integrin alpha-RLC; ALPHA-RLC; Entrez Gene ID 3680 Protein Refseq NP_002198 UniProt ID Q13797 Chromosome Location 3p21.3 Pathway Arrhythmogenic right ventricular cardiomyopathy (ARVC), organism-specific biosystem; Arrhythmogenic right ventricular cardiomyopathy (ARVC), conserved biosystem; Axon guidance, organism-specific biosystem; Cell adhesion molecules (CAMs), organism-specific biosystem; Cell adhesion molecules (CAMs), conserved biosystem; Developmental Biology, organism- specific biosystem; Dilated cardiomyopathy, organism-specific biosystem.
    [Show full text]
  • Table 3: Average Gene Expression Profiles by Chromosome
    Supplemental Data Table 1: Experimental Setup Correlation Array Reverse Fluor Array Extraction Coefficient Print Batch (Y/N) mean (range) DLD1-I.1 I A N DLD1-I.2 I B N 0.86 DLD1-I.3 I C N (0.79-0.90) DLD1-I.4 I C Y DLD1 DLD1-II.1 II D N DLD1-II.2 II E N 0.86 DLD1-II.3 II F N (0.74-0.94) DLD1-II.4 II F Y DLD1+3-II.1 II A N DLD1+3-II.2 II A N 0.85 DLD1 + 3 DLD1+3-II.3 II B N (0.64-0.95) DLD1+3-II.4 II B Y DLD1+7-I.1 I A N DLD1+7-I.2 I A N 0.79 DLD1 + 7 DLD1+7-I.3 I B N (0.68-0.90) DLD1+7-I.4 I B Y DLD1+13-I.1 I A N DLD1+13-I.2 I A N 0.88 DLD1 + 13 DLD1+13-I.3 I B N (0.84-0.91) DLD1+13-I.4 I B Y hTERT-HME-I.1 I A N hTERT-HME-I.2 I B N 0.85 hTERT-HME hTERT-HME-I.3 I C N (0.80-0.92) hTERT-HME-I.4 I C Y hTERT-HME+3-I.1 I A N hTERT-HME+3-I.2 I B N 0.84 hTERT-HME + 3 hTERT-HME+3-I.3 I C N (0.74-0.90) hTERT-HME+3-I.4 I C Y Supplemental Data Table 2: Average gene expression profiles by chromosome arm DLD1 hTERT-HME Ratio.7 Ratio.1 Ratio.3 Ratio.3 Chrom.
    [Show full text]
  • Integrin Alpha 9 Antibody Product Data Sheet Tested Species Reactivity Details Human (Hu) Catalog Number: PA5-27771
    Lot Number: QE2031191G Integrin alpha 9 Antibody Product Data Sheet Tested Species Reactivity Details Human (Hu) Catalog Number: PA5-27771 Size: 100 µL Tested Applications Dilution * Class: Polyclonal Western Blot (WB) 1:500-1:3000 Type: Antibody Immunohistochemistry (Paraffin) 1:100-1:1000 Clone: (IHC (P)) Host / Isotype: Rabbit / IgG * Suggested working dilutions are given as a guide only. It is recommended that the user titrates the product for use in their own experiment using appropriate negative and positive controls. Recombinant fragment corresponding to a region within Immunogen: amino acids 1 and 255 of Human Integrin alpha 9 Form Information Form: Liquid Concentration: 1mg/ml Purification: Antigen affinity chromatography PBS, pH 7, with 1% BSA, 20% Storage Buffer: glycerol Preservative: 0.01% thimerosal Storage Conditions: -20° C, Avoid Freeze/Thaw Cycles Product Specific Information General Information PA5-27771 targets Integrin alpha 9 in IHC (P) and WB applications and This gene encodes an alpha integrin. Integrins are heterodimeric integral shows reactivity with Human samples. membrane glycoproteins composed of an alpha chain and a beta chain that mediate cell-cell and cell-matrix adhesion. The protein encoded by this gene, The PA5-27771 immunogen is recombinant fragment corresponding to a when bound to the beta 1 chain, forms an integrin that is a receptor for region within amino acids 1 and 255 of Human Integrin alpha 9. VCAM1, cytotactin and osteopontin. Expression of this gene has been found For Research Use Only. Not for use in diagnostic procedures. Not for to be upregulated in small cell lung cancers. resale without express authorization.
    [Show full text]
  • Anti-ITGB1 Monoclonal Antibody, Clone 4C7 (DCABH-1896) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use
    Anti-ITGB1 monoclonal antibody, clone 4C7 (DCABH-1896) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Product Overview Mouse monoclonal to Integrin beta 1 Antigen Description Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Integrins alpha-2/beta-1, alpha-3/beta-1, alpha-4/beta-1, alpha-5/beta-1, alpha-8/beta-1, alpha-10/beta-1, alpha-11/beta-1 and alpha-V/beta-1 are receptors for fibronectin. Alpha-4/beta-1 recognizes one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1 is a receptor for fibrinogen. Integrin alpha-1/beta-1, alpha-2/beta-1, alpha-6/beta-1 and alpha-7/beta-1 are receptors for lamimin. Integrin alpha-4/beta-1 is a receptor for VCAM1. It recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. Integrin alpha-3/beta-1 is a receptor for epiligrin, thrombospondin and CSPG4. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. Integrin alpha-V/beta-1 is a receptor for vitronectin. Beta-1 integrins recognize the sequence R-G-D in a wide array of ligands.
    [Show full text]
  • Integrin and Gene Network Analysis Reveals That ITGA5 and ITGB1 Are Prognostic in Non-Small-Cell Lung Cancer
    Journal name: OncoTargets and Therapy Article Designation: Original Research Year: 2016 Volume: 9 OncoTargets and Therapy Dovepress Running head verso: Zheng et al Running head recto: ITGA5 and ITGB1 are prognostic in NSCLC open access to scientific and medical research DOI: http://dx.doi.org/10.2147/OTT.S91796 Open Access Full Text Article ORIGINAL RESEARCH Integrin and gene network analysis reveals that ITGA5 and ITGB1 are prognostic in non-small-cell lung cancer Weiqi Zheng Background: Integrin expression has been identified as a prognostic factor in non-small-cell Caihui Jiang lung cancer (NSCLC). This study was aimed at determining the predictive ability of integrins Ruifeng Li and associated genes identified within the molecular network. Patients and methods: A total of 959 patients with NSCLC from The Cancer Genome Atlas Department of Radiation Oncology, Guangqian Hospital, Quanzhou, Fujian, cohorts were enrolled in this study. The expression profile of integrins and related genes were People’s Republic of China obtained from The Cancer Genome Atlas RNAseq database. Clinicopathological characteristics, including age, sex, smoking history, stage, histological subtype, neoadjuvant therapy, radiation therapy, and overall survival (OS), were collected. Cox proportional hazards regression models as well as Kaplan–Meier curves were used to assess the relative factors. Results: In the univariate Cox regression model, ITGA1, ITGA5, ITGA6, ITGB1, ITGB4, and ITGA11 were predictive of NSCLC prognosis. After adjusting for clinical factors, ITGA5 (odds ratio =1.17, 95% confidence interval: 1.05–1.31) andITGB1 (odds ratio =1.31, 95% confidence interval: 1.10–1.55) remained statistically significant. In the gene cluster network analysis, PLAUR, ILK, SPP1, PXN, and CD9, all associated with ITGA5 and ITGB1, were identified as independent predictive factors of OS in NSCLC.
    [Show full text]
  • Single-Cell Landscape of Bronchoalveolar Immune Cells in Patients with COVID-19
    BRIEF COMMUNICATION https://doi.org/10.1038/s41591-020-0901-9 Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19 Mingfeng Liao1,6, Yang Liu1,6, Jing Yuan2,6, Yanling Wen1, Gang Xu1, Juanjuan Zhao1, Lin Cheng1, Jinxiu Li2, Xin Wang1, Fuxiang Wang2, Lei Liu1,3 ✉ , Ido Amit 4 ✉ , Shuye Zhang 5 ✉ and Zheng Zhang 1,3 ✉ Respiratory immune characteristics associated with The macrophage compartments differed largely in both compo- Coronavirus Disease 2019 (COVID-19) severity are cur- sition and expression of FCN1, SPP1 and FABP4 in different cell rently unclear. We characterized bronchoalveolar lavage fluid groups (Fig. 1c and Extended Data Fig. 2d). FABP4 was prefer- immune cells from patients with varying severity of COVID-19 entially expressed by controls and patients with moderate infec- and from healthy people by using single-cell RNA sequencing. tion, while FCN1 and SPP1 were highly expressed by patients Proinflammatory monocyte-derived macrophages were abun- with severe/critical infection (Fig. 1d). We conducted differen- dant in the bronchoalveolar lavage fluid from patients with tially expressed gene (DEG) analysis (Extended Data Fig. 2e), gene severe COVID-9. Moderate cases were characterized by the ontology (GO) analysis and gene set enrichment analysis (GSEA) presence of highly clonally expanded CD8+ T cells. This atlas (Extended Data Fig. 2f) between cell groups. Group 1 expressed of the bronchoalveolar immune microenvironment suggests the peripheral monocyte-like markers S100A8, FCN1 and CD14, potential mechanisms underlying pathogenesis and recovery and group 2 expressed high levels of the chemokines CCL2, CCL3, in COVID-19. CXCL10 and other genes.
    [Show full text]
  • COMPREHENSIVE INVITED REVIEW Chemokines and Their Receptors
    COMPREHENSIVE INVITED REVIEW Chemokines and Their Receptors Are Key Players in the Orchestra That Regulates Wound Healing Manuela Martins-Green,* Melissa Petreaca, and Lei Wang Department of Cell Biology and Neuroscience, University of California, Riverside, California. Significance: Normal wound healing progresses through a series of over- lapping phases, all of which are coordinated and regulated by a variety of molecules, including chemokines. Because these regulatory molecules play roles during the various stages of healing, alterations in their presence or function can lead to dysregulation of the wound-healing process, potentially leading to the development of chronic, nonhealing wounds. Recent Advances: A discovery that chemokines participate in a variety of disease conditions has propelled the study of these proteins to a level that potentially could lead to new avenues to treat disease. Their small size, ex- posed termini, and the fact that their only modifications are two disulfide Manuela Martins-Green, PhD bonds make them excellent targets for manipulation. In addition, because they bind to G-protein-coupled receptors (GPCRs), they are highly amenable to Submitted for publication January 9, 2013. *Correspondence: Department of Cell Biology pharmacological modulation. and Neuroscience, University of California, Riv- Critical Issues: Chemokines are multifunctional, and in many situations, their erside, Biological Sciences Building, 900 Uni- functions are highly dependent on the microenvironment. Moreover, each versity Ave., Riverside, CA 92521 (email: [email protected]). specific chemokine can bind to several GPCRs to stimulate the function, and both can function as monomers, homodimers, heterodimers, and even oligo- mers. Activation of one receptor by any single chemokine can lead to desen- Abbreviations sitization of other chemokine receptors, or even other GPCRs in the same cell, and Acronyms with implications for how these proteins or their receptors could be used to Ang-2 = angiopoietin-2 manipulate function.
    [Show full text]