DOCSLIB.ORG

Complex-Mediated Glomerulonephritis Inflammation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Complex-Mediated Glomerulonephritis Inflammation Mouse Mast Cell Protease-4 Deteriorates Renal Function by Contributing to Inflammation and Fibrosis in Immune Complex-Mediated Glomerulonephritis This information is current as of October 1, 2021. Lisa Scandiuzzi, Walid Beghdadi, Eric Daugas, Magnus Åbrink, Neeraj Tiwari, Cristiana Brochetta, Julien Claver, Nassim Arouche, Xingxing Zang, Marina Pretolani, Renato C. Monteiro, Gunnar Pejler and Ulrich Blank J Immunol published online 7 June 2010 Downloaded from http://www.jimmunol.org/content/early/2010/06/07/jimmun ol.0902129 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 October 1, 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 All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published June 7, 2010, doi:10.4049/jimmunol.0902129 The Journal of Immunology Mouse Mast Cell Protease-4 Deteriorates Renal Function by Contributing to Inflammation and Fibrosis in Immune Complex-Mediated Glomerulonephritis Lisa Scandiuzzi,*,†,1 Walid Beghdadi,*,† Eric Daugas,*,†,‡ Magnus A˚ brink,x Neeraj Tiwari,*,† Cristiana Brochetta,*,† Julien Claver,*,† Nassim Arouche,†,{ Xingxing Zang,|| Marina Pretolani,†,{ Renato C. Monteiro,*,† Gunnar Pejler,# and Ulrich Blank*,† Mast cells exert protective effects in experimental antiglomerular basement membrane-induced glomerulonephritis (GN), yet the responsible mediators have not been identified. In this study, we investigated the role of mouse mast cell protease (mMCP)-4, the functional homolog of human chymase, using mMCP-4–deficient mice. Compared with wild type animals, mMCP-4–deficient mice Downloaded from exhibited lower proteinuria, blood creatinine, and blood urea nitrogen levels, indicating an aggravating role of mMCP-4. Kidney histology confirmed less severe renal damage in mMCP-4–deficient mice with reduced deposits, glomerular and interstitial cellularity, and fibrosis scores. High amounts of mMCP-4 were detected in renal capsules, but not in the whole kidney, from wild type mice. Its expression in renal capsules was markedly decreased after GN induction, suggesting that locally released enzyme by degranulated mast cells could contribute to the functional and physiopathological hallmarks of GN. Supporting a proinflammatory role, glomerular and interstitial macrophage and T cell infiltration, levels of proinflammatory TNF and http://www.jimmunol.org/ MCP-1 mRNA, and the expression of the profibrotic peptide angiotensin II together with type I collagen were markedly down- regulated in kidneys of mMCP-42deficient mice. We conclude that mMCP-4 chymase, contrary to the global anti-inflammatory action of mast cells, aggravates GN by promoting kidney inflammation. These results highlight the complexity of mast cell- mediated inflammatory actions and suggest that chymase inhibition may represent a novel therapeutic target in GN. The Journal of Immunology, 2010, 185: 000–000. ast cells are key effectors of innate and adaptive im- granules, and most of them are present exclusively in mast cells. munity (1–3). Upon activation, they produce numerous These proteases can be divided into three classes: tryptases, car- by guest on October 1, 2021 M inflammatory mediators released from cytoplasmic boxypeptidase A, and chymases, all of which are released in granules or after new synthesis, including arachidonic acid a complex with negatively charged serglycin proteoglycans (5–7). metabolites and a diverse set of cytokines and chemokines (3, 4). Chymases are chymotrypsin-like serine proteases, which can be Neutral proteases are contained in high amounts in the cytoplasmic classified into a-chymases and b-chymases, according to their biochemical structure (5–7). Human mast cells express only one a-chymase, whereas rodents express one a-chymase, mouse mast † b *Institut National de la Sante´ et de la Recherche Me´dicale U699; Universite´ Paris 7, cell protease (mMCP)-5, and several -chymases, including Faculte´ de Me´decine Paris Diderot-Site Xavier Bichat; ‡Service de Ne´phrologie, Groupe mMCP-1, -2, and -4. While mMCP-4 and -5 are specifically Hospitalier Universitaire Bichat-Claude Bernard, Assistance Publique-Hoˆpitaux de Paris; { x expressed by mast cells in connective tissues, mMCP-1 and -2 Institut National de la Sante´ et de la Recherche Me´dicale U700, Paris, France; De- partment of Medical Biochemistry and Microbiology, Uppsala University; #Department are found in mucosal subtype mast cells. The former are stored of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, in tight complexes with serglycin proteoglycans and are released Uppsala, Sweden; and ||Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY 10461 only upon degranulation, whereas the latter have low affinity for 1 serglycin proteoglycans and, accordingly, they may be constitu- Current address: Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY. tively secreted (8). Among the murine chymases, mMCP-4 is most Received for publication July 7, 2009. Accepted for publication April 21, 2010. likely the functional counterpart of the unique human chymase This work was supported by the French National Research Agency (R08171HS), the because it has similar substrate specificity, tissue distribution, ser- Fondation pour la Recherche Me´dicale, the Association pour l’Utilisation du Rein glycin proteoglycan-binding properties, and ability to convert an- Artificiel, and the Marie Curie Early Stage Research Training Fellowship of the giotensin (Ang) I into Ang II (5, 9, 10). European Community’s Sixth Framework Programme under contract no. 504926. In addition to their crucial role in allergy and asthma, mast cells Address correspondence and reprint requests to: Dr. Ulrich Blank, Institut National de la Sante´ et de la Recherche Me´dicale U699, Universite´ Paris 7, Faculte´ de Me´de- have recently been associated with renal diseases, because their cine Denis Diderot, Site Xavier Bichat, 16 Rue Henri Huchard, 75780 Paris Cedex numbers are strongly increased in nephropathies of different origins 18, France. E-mail address: [email protected] (11–13). Functional studies conducted using mast cell-deficient mice Abbreviations used in this paper: ACE, angiotensin-converting enzyme; Ang, angio- revealed protective properties of mast cells in an accelerated model tensin; anti-GBM, antiglomerular basement membrane; BMDM, bone marrow- derived macrophage; BMMC, bone marrow-derived mast cell; BUN, blood urea of antiglomerular basement membrane (anti-GBM)–induced glo- nitrogen; DTH, delayed-type hypersensitivity; GN, glomerulonephritis; mMCP, merulonephritis (GN), most likely through their capacity to initiate mouse mast cell protease; NRS, normal rabbit serum; PAS, periodic acid-Schiff; repair and remodeling and to favorably influence immune responses RT, room temperature; SA, streptavidin; WT, wild type. (14, 15). However, other results demonstrated a detrimental role in Copyright Ó 2010 by The American Association of Immunologists, Inc. 0022-1767/10/$16.00 a nonaccelerated disease model of kidney disease (16). In this model, www.jimmunol.org/cgi/doi/10.4049/jimmunol.0902129 2 AGGRAVATING ROLE OF mMCP-4 CHYMASE IN GLOMERULONEPHRITIS mast cells promoted glomerular expression of adhesion molecules 8.7, 16.9 6 10.2, and 13.7 6 4.8; and for kidney capsules: 4.7 6 2.3, and enhanced Th1-dependent effector mechanisms. Overall, these 4.8 6 1.5, 1.8 6 1.3, and 1.2 6 0.7. observations indicate that mast cells can exert beneficial or detri- mental activities, depending on a given pathophysiological context. Induction of anti-GBM–induced GN Therefore, further studies are needed to clarify the mechanisms by Anti-GBM serum was produced in rabbits following immunization with pu- which mast cells affect renal disease parameters. rified mouse glomeruli obtained according to established procedures (22). The murine counterpart of human mast cell chymase, mMCP-4, An accelerated model of anti-GBM Ab-induced GN was used (23, 24). was shown to attract granulocytes and macrophages (17, 18), to Briefly, mice were preimmunized i.p. with normal rabbit IgG (0.5 mg/20 g regulate homeostatic intestinal epithelial migration and barrier body weight) (Southern Biotechnology Associates) and CFA (Sigma- function (19), and to convert Ang I into Ang II, a vasoactive peptide Aldrich) 5 d before an i.v. administration of anti-GBM serum through the retro-orbital vein at a dose of 0.2 ml/20 g. For control purposes, with potent inflammatory and fibrogenic properties (20, 21). These NRS was also used. Mice were sacrificed at day 3 to evaluate early changes observations suggest that mMCP-4 may play an important role in of the heterologous phase following deposition of rabbit anti-GBM or at tissue inflammation and remodeling in the kidney. To explore this day 14 to evaluate late changes provoked by the developing immune re- issue, we examined
Load more

Recommended publications
  • Serine Proteases with Altered Sensitivity to Activity-Modulating
    (19) & (11) EP 2 045 321 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 08.04.2009 Bulletin 2009/15 C12N 9/00 (2006.01) C12N 15/00 (2006.01) C12Q 1/37 (2006.01) (21) Application number: 09150549.5 (22) Date of filing: 26.05.2006 (84) Designated Contracting States: • Haupts, Ulrich AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 51519 Odenthal (DE) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • Coco, Wayne SK TR 50737 Köln (DE) •Tebbe, Jan (30) Priority: 27.05.2005 EP 05104543 50733 Köln (DE) • Votsmeier, Christian (62) Document number(s) of the earlier application(s) in 50259 Pulheim (DE) accordance with Art. 76 EPC: • Scheidig, Andreas 06763303.2 / 1 883 696 50823 Köln (DE) (71) Applicant: Direvo Biotech AG (74) Representative: von Kreisler Selting Werner 50829 Köln (DE) Patentanwälte P.O. Box 10 22 41 (72) Inventors: 50462 Köln (DE) • Koltermann, André 82057 Icking (DE) Remarks: • Kettling, Ulrich This application was filed on 14-01-2009 as a 81477 München (DE) divisional application to the application mentioned under INID code 62. (54) Serine proteases with altered sensitivity to activity-modulating substances (57) The present invention provides variants of ser- screening of the library in the presence of one or several ine proteases of the S1 class with altered sensitivity to activity-modulating substances, selection of variants with one or more activity-modulating substances. A method altered sensitivity to one or several activity-modulating for the generation of such proteases is disclosed, com- substances and isolation of those polynucleotide se- prising the provision of a protease library encoding poly- quences that encode for the selected variants.
    [Show full text]
  • For Serine Proteas
    Ribeiro et al. BMC Structural Biology 2010, 10:36 http://www.biomedcentral.com/1472-6807/10/36 METHODOLOGY ARTICLE Open Access Analysis of binding properties and specificity through identification of the interface forming residues (IFR) for serine proteases in silico docked to different inhibitors Cristina Ribeiro1†, Roberto C Togawa2†, Izabella AP Neshich3, Ivan Mazoni3, Adauto L Mancini3, Raquel C de Melo Minardi5, Carlos H da Silveira4, José G Jardine3, Marcelo M Santoro1, Goran Neshich3* Abstract Background: Enzymes belonging to the same super family of proteins in general operate on variety of substrates and are inhibited by wide selection of inhibitors. In this work our main objective was to expand the scope of studies that consider only the catalytic and binding pocket amino acids while analyzing enzyme specificity and instead, include a wider category which we have named the Interface Forming Residues (IFR). We were motivated to identify those amino acids with decreased accessibility to solvent after docking of different types of inhibitors to sub classes of serine proteases and then create a table (matrix) of all amino acid positions at the interface as well as their respective occupancies. Our goal is to establish a platform for analysis of the relationship between IFR characteristics and binding properties/specificity for bi-molecular complexes. Results: We propose a novel method for describing binding properties and delineating serine proteases specificity by compiling an exhaustive table of interface forming residues (IFR) for serine proteases and their inhibitors. Currently, the Protein Data Bank (PDB) does not contain all the data that our analysis would require. Therefore, an in silico approach was designed for building corresponding complexes The IFRs are obtained by “rigid body docking” among 70 structurally aligned, sequence wise non-redundant, serine protease structures with 3 inhibitors: bovine pancreatic trypsin inhibitor (BPTI), ecotine and ovomucoid third domain inhibitor.
    [Show full text]
  • Proteolytic Enzymes in Grass Pollen and Their Relationship to Allergenic Proteins
    Proteolytic Enzymes in Grass Pollen and their Relationship to Allergenic Proteins By Rohit G. Saldanha A thesis submitted in fulfilment of the requirements for the degree of Masters by Research Faculty of Medicine The University of New South Wales March 2005 TABLE OF CONTENTS TABLE OF CONTENTS 1 LIST OF FIGURES 6 LIST OF TABLES 8 LIST OF TABLES 8 ABBREVIATIONS 8 ACKNOWLEDGEMENTS 11 PUBLISHED WORK FROM THIS THESIS 12 ABSTRACT 13 1. ASTHMA AND SENSITISATION IN ALLERGIC DISEASES 14 1.1 Defining Asthma and its Clinical Presentation 14 1.2 Inflammatory Responses in Asthma 15 1.2.1 The Early Phase Response 15 1.2.2 The Late Phase Reaction 16 1.3 Effects of Airway Inflammation 16 1.3.1 Respiratory Epithelium 16 1.3.2 Airway Remodelling 17 1.4 Classification of Asthma 18 1.4.1 Extrinsic Asthma 19 1.4.2 Intrinsic Asthma 19 1.5 Prevalence of Asthma 20 1.6 Immunological Sensitisation 22 1.7 Antigen Presentation and development of T cell Responses. 22 1.8 Factors Influencing T cell Activation Responses 25 1.8.1 Co-Stimulatory Interactions 25 1.8.2 Cognate Cellular Interactions 26 1.8.3 Soluble Pro-inflammatory Factors 26 1.9 Intracellular Signalling Mechanisms Regulating T cell Differentiation 30 2 POLLEN ALLERGENS AND THEIR RELATIONSHIP TO PROTEOLYTIC ENZYMES 33 1 2.1 The Role of Pollen Allergens in Asthma 33 2.2 Environmental Factors influencing Pollen Exposure 33 2.3 Classification of Pollen Sources 35 2.3.1 Taxonomy of Pollen Sources 35 2.3.2 Cross-Reactivity between different Pollen Allergens 40 2.4 Classification of Pollen Allergens 41 2.4.1
    [Show full text]
  • Associations Between the Complement System and Choroidal Neovascularization in Wet Age-Related Macular Degeneration
    International Journal of Molecular Sciences Review Associations between the Complement System and Choroidal Neovascularization in Wet Age-Related Macular Degeneration 1 2 1 1, Emilie Grarup Jensen , Thomas Stax Jakobsen , Steffen Thiel , Anne Louise Askou y 1,2, , and Thomas J. Corydon * y 1 Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark; [email protected] (E.G.J.); [email protected] (S.T.); [email protected] (A.L.A.) 2 Department of Ophthalmology, Aarhus University Hospital, 8200 Aarhus N, Denmark; [email protected] * Correspondence: [email protected]; Tel.: +45-28-99-21-79 These authors contributed equally to this work. y Received: 18 November 2020; Accepted: 17 December 2020; Published: 21 December 2020 Abstract: Age-related macular degeneration (AMD) is the leading cause of blindness affecting the elderly in the Western world. The most severe form of AMD, wet AMD (wAMD), is characterized by choroidal neovascularization (CNV) and acute vision loss. The current treatment for these patients comprises monthly intravitreal injections of anti-vascular endothelial growth factor (VEGF) antibodies, but this treatment is expensive, uncomfortable for the patient, and only effective in some individuals. AMD is a complex disease that has strong associations with the complement system. All three initiating complement pathways may be relevant in CNV formation, but most evidence indicates a major role for the alternative pathway (AP) and for the terminal complement complex, as well as certain complement peptides generated upon complement activation. Since the complement system is associated with AMD and CNV, a complement inhibitor may be a therapeutic option for patients with wAMD.
    [Show full text]
  • Trypsin-Like Proteases and Their Role in Muco-Obstructive Lung Diseases
    International Journal of Molecular Sciences Review Trypsin-Like Proteases and Their Role in Muco-Obstructive Lung Diseases Emma L. Carroll 1,†, Mariarca Bailo 2,†, James A. Reihill 1 , Anne Crilly 2 , John C. Lockhart 2, Gary J. Litherland 2, Fionnuala T. Lundy 3 , Lorcan P. McGarvey 3, Mark A. Hollywood 4 and S. Lorraine Martin 1,* 1 School of Pharmacy, Queen’s University, Belfast BT9 7BL, UK; [email protected] (E.L.C.); [email protected] (J.A.R.) 2 Institute for Biomedical and Environmental Health Research, School of Health and Life Sciences, University of the West of Scotland, Paisley PA1 2BE, UK; [email protected] (M.B.); [email protected] (A.C.); [email protected] (J.C.L.); [email protected] (G.J.L.) 3 Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University, Belfast BT9 7BL, UK; [email protected] (F.T.L.); [email protected] (L.P.M.) 4 Smooth Muscle Research Centre, Dundalk Institute of Technology, A91 HRK2 Dundalk, Ireland; [email protected] * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Trypsin-like proteases (TLPs) belong to a family of serine enzymes with primary substrate specificities for the basic residues, lysine and arginine, in the P1 position. Whilst initially perceived as soluble enzymes that are extracellularly secreted, a number of novel TLPs that are anchored in the cell membrane have since been discovered. Muco-obstructive lung diseases (MucOLDs) are Citation: Carroll, E.L.; Bailo, M.; characterised by the accumulation of hyper-concentrated mucus in the small airways, leading to Reihill, J.A.; Crilly, A.; Lockhart, J.C.; Litherland, G.J.; Lundy, F.T.; persistent inflammation, infection and dysregulated protease activity.
    [Show full text]
  • 31 Antiphospholipid Antibody–Induced Pregnancy Loss and Thrombosis Guillermina Girardi and Jane E
    31 Antiphospholipid Antibody–Induced Pregnancy Loss and Thrombosis Guillermina Girardi and Jane E. Salmon Antiphospholipid (aPL) antibodies are a family of autoantibodies that exhibit a broad range of target specificities and affinities, all recognizing various combina- tions of phospholipids, phospholipid binding proteins, or both. The first aPL anti- body, a complement fixing antibody that reacted with extracts from bovine hearts, was detected in patients with syphilis in 1906 [1]. The relevant antigen was later identified as cardiolipin, a mitochondrial phospholipid [2]. The presence of aPL antibodies in serum has been associated with arterial and venous thrombosis and recurrent pregnancy loss [3–7], but the pathogenic mechanisms mediating these events are unknown. Several hypotheses have been proposed to explain the cellular and molecular mechanisms by which aPL antibodies induce thrombosis and fetal loss. There are reports that aPL antibodies activate endothelial cells, monocytes, and platelets [8–10]. In vivo and in vitro studies have shown that exposure to aPL antibodies induces activation of endothelial cells and a prothrombotic phenotype, as assessed by upregulation of the expression of adhesion molecules, secretion of cytokines, and the metabolism of prostacyclins [8, 10, 11]. aPL antibodies recognize β 2-glycoprotein I bound to resting endothelial cells, although the basis for the inter- β action of 2-glycoprotein I with viable endothelial cells remains unclear [12, 13]. As β 2-glycoprotein I is considered a natural anticoagulant [14], some authors propose that aPL antibodies interfere with or modulate the function of phospholipid binding proteins involved in the regulation of coagulation, activate platelets, or induce monocytes to express tissue factor [9].
    [Show full text]
  • Hereditary Alpha Tryptasemia, Mastocytosis and Beyond
    International Journal of Molecular Sciences Review Genetic Regulation of Tryptase Production and Clinical Impact: Hereditary Alpha Tryptasemia, Mastocytosis and Beyond Bettina Sprinzl 1,2, Georg Greiner 3,4,5 , Goekhan Uyanik 1,2,6, Michel Arock 7,8 , Torsten Haferlach 9, Wolfgang R. Sperr 4,10, Peter Valent 4,10 and Gregor Hoermann 4,9,* 1 Ludwig Boltzmann Institute for Hematology and Oncology at the Hanusch Hospital, Center for Medical Genetics, Hanusch Hospital, 1140 Vienna, Austria; [email protected] (B.S.); [email protected] (G.U.) 2 Center for Medical Genetics, Hanusch Hospital, 1140 Vienna, Austria 3 Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria; [email protected] 4 Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, 1090 Vienna, Austria; [email protected] (W.R.S.); [email protected] (P.V.) 5 Ihr Labor, Medical Diagnostic Laboratories, 1220 Vienna, Austria 6 Medical School, Sigmund Freud Private University, 1020 Vienna, Austria 7 Department of Hematology, APHP, Pitié-Salpêtrière-Charles Foix University Hospital and Sorbonne University, 75013 Paris, France; [email protected] 8 Centre de Recherche des Cordeliers, INSERM, Sorbonne University, Cell Death and Drug Resistance in Hematological Disorders Team, 75006 Paris, France 9 MLL Munich Leukemia Laboratory, 81377 Munich, Germany; [email protected] 10 Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, 1090 Vienna, Austria * Correspondence: [email protected]; Tel.: +49-89-99017-315 Citation: Sprinzl, B.; Greiner, G.; Uyanik, G.; Arock, M.; Haferlach, T.; Abstract: Tryptase is a serine protease that is predominantly produced by tissue mast cells (MCs) and Sperr, W.R.; Valent, P.; Hoermann, G.
    [Show full text]
  • 12) United States Patent (10
    US007635572B2 (12) UnitedO States Patent (10) Patent No.: US 7,635,572 B2 Zhou et al. (45) Date of Patent: Dec. 22, 2009 (54) METHODS FOR CONDUCTING ASSAYS FOR 5,506,121 A 4/1996 Skerra et al. ENZYME ACTIVITY ON PROTEIN 5,510,270 A 4/1996 Fodor et al. MICROARRAYS 5,512,492 A 4/1996 Herron et al. 5,516,635 A 5/1996 Ekins et al. (75) Inventors: Fang X. Zhou, New Haven, CT (US); 5,532,128 A 7/1996 Eggers Barry Schweitzer, Cheshire, CT (US) 5,538,897 A 7/1996 Yates, III et al. s s 5,541,070 A 7/1996 Kauvar (73) Assignee: Life Technologies Corporation, .. S.E. al Carlsbad, CA (US) 5,585,069 A 12/1996 Zanzucchi et al. 5,585,639 A 12/1996 Dorsel et al. (*) Notice: Subject to any disclaimer, the term of this 5,593,838 A 1/1997 Zanzucchi et al. patent is extended or adjusted under 35 5,605,662 A 2f1997 Heller et al. U.S.C. 154(b) by 0 days. 5,620,850 A 4/1997 Bamdad et al. 5,624,711 A 4/1997 Sundberg et al. (21) Appl. No.: 10/865,431 5,627,369 A 5/1997 Vestal et al. 5,629,213 A 5/1997 Kornguth et al. (22) Filed: Jun. 9, 2004 (Continued) (65) Prior Publication Data FOREIGN PATENT DOCUMENTS US 2005/O118665 A1 Jun. 2, 2005 EP 596421 10, 1993 EP 0619321 12/1994 (51) Int. Cl. EP O664452 7, 1995 CI2O 1/50 (2006.01) EP O818467 1, 1998 (52) U.S.
    [Show full text]
  • Β-Tryptase and Complement Fractions C3-C4 Are the Indispensable Working Tools
    Int. J. Mol. Sci. 2015, 16, 6557-6570; doi:10.3390/ijms16036557 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Review Amniotic Fluid Embolism Pathophysiology Suggests the New Diagnostic Armamentarium: β-Tryptase and Complement Fractions C3-C4 Are the Indispensable Working Tools Francesco Paolo Busardò 1, Paola Frati 1,2, Simona Zaami 1 and Vittorio Fineschi 1,* 1 Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy; E-Mails: [email protected] (F.P.B.); [email protected] (S.Z.) 2 Neuromed, Istituto Mediterraneo Neurologico (IRCCS), Via Atinense 18, Pozzilli, 86077 Isernia, Italy; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +39-06-49912722; Fax: +39-06-445535. Academic Editor: Robert J. Norman Received: 26 December 2014 / Accepted: 10 March 2015 / Published: 23 March 2015 Abstract: Amniotic fluid embolism (AFE) is an uncommon obstetric condition involving pregnant women during labor or in the initial stages after delivery. Its incidence is estimated to be around 5.5 cases per 100,000 deliveries. Therefore, this paper investigated the pathophysiological mechanism, which underlies AFE, in order to evaluate the role of immune response in the development of this still enigmatic clinical entity. The following databases (from 1956 to September 2014) Medline, Cochrane Central, Scopus, Web of Science and Science Direct were used, searching the following key words: AFE, pathophysiology, immune/inflammatory response, complement and anaphylaxis. The main key word “AFE” was searched singularly and associated individually to each of the other keywords.
    [Show full text]
  • Cleavage Specificity and Biochemical Characterization of Mast Cell Serine Proteases
    Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 870 Cutting Edge – Cleavage Specificity and Biochemical Characterization of Mast Cell Serine Proteases BY ULRIKA KARLSON ACTA UNIVERSITATIS UPSALIENSIS UPPSALA 2003 !" # $ $ % & " ' & & (" ") !" * + '") , ) $) ' +' - ' . & " " / & 0 . ( ) 1 ) 23) ) ) 4.5 %6768%%6 4 * " " 90: * " ' " ' " " * " & ') 0 " ; & ' ' & 0 & ) !* ; ' & 0 " < " *"" ' & & *"" & & " ' ) " " / & " & * ' " 0 & ) # & " " " " ' & & * 0 " 90(:67 0(6) !" & * / ' " ' " = *"" ' & ' ) !" " 0(67 ' & * " ' & & * = 56 & " ' ) !" " "& " ' & & " " ) " ' " ' = & ' ' & 0(67 " " >?@444 " !A>B ) !" " ' " = * / " & & 0(6) 0(6 " " = " " ) 4 ' 0(6 " " * " * " / & " & ) 0(6 " " '" "& " && ' & ) !" & ' & & " " && & & * & * ' ' & ) !" 0 " 6 & & " 0) ! " = & & 0(68 0(68 * ) 1 * C 9D8): * ' " ' ' )') " * " * " ) E " " " ' * & " " 0(68 " ) 4 " " ' * " * "'" && " ) !" " ' '" ' & " ' " ) " & " ' ! " # ! #$ %&'! #"! ! ()*%+,- ! F , $ 4..5 76$$G 4.5 %6768%%6
    [Show full text]
  • Granzyme a in the Pathogenesis of Type 1 Diabetes: the Yes and the No
    Diabetes Volume 66, December 2017 2937 Granzyme A in the Pathogenesis of Type 1 Diabetes: The Yes and the No Thomas Mandrup-Poulsen Diabetes 2017;66:2937–2939 | https://doi.org/10.2337/dbi17-0037 Two major unanswered questions related to the pathogen- GrzmA, discovered by Tschopp and colleagues (9) in esis of type 1 diabetes (T1D) prevent progress in our ability 1986, belongs to the granzyme family of serine proteases to intervene in disease development: What breaks immune encompassing 10 members in the mouse and 5 members in tolerance to the pancreatic b-cells? And what kills the the human (10,11). They have trypsin-, chymotrypsin-, and b-cells? elastase-like proteolytic activities, but in contrast to these By the surprising demonstration that knockout of the broad serine proteases, granzymes have higher substrate tryptase granzyme A (GrzmA), conventionally considered to specificity conferred by a substrate binding pocket. Gran- be a key proapoptotic mediator of immune killer cell cyto- zymes are expressed mainly in cytotoxic T cells and natural toxicity, does not protect but markedly accelerates and in- killer (NK) cells in response to interleukin (IL)-2 in synergy creases incidence of T1D in the nonobese diabetic (NOD) with IL-12 (12,13), with GrzmA being the most abundantly mouse, Mollah et al. (1) add to answering both of these expressed but also having lower cytotoxic activity than questions. On one hand, they show that GrzmA does not GrzmB. GrzmA and GrzmB are also expressed in gdT cells, COMMENTARY contribute to b-cell killing. On the other hand, their striking a subset of the intraepithelial lymphocytes abundant in the finding that diabetes resistance in the proinsulin II trans- intestinal mucosa, and in thymocytes, suggesting roles in genic mouse is broken by GrzmA knockout provides evi- both central tolerance and gut immunity.
    [Show full text]
  • A Role of a Lymphocyte Tryptase, Granzyme A, in Experimental Ulcerative Colitis
    Biosci. Biotechnol. Biochem., 71 (1), 234–237, 2007 Note A Role of a Lymphocyte Tryptase, Granzyme A, in Experimental Ulcerative Colitis y Hirofumi HIRAYASU,* Yumiko YOSHIKAWA,* Satoshi TSUZUKI, and Tohru FUSHIKI Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan Received June 23, 2006; Accepted October 4, 2006; Online Publication, January 7, 2007 [doi:10.1271/bbb.60354] In the large-intestinal mucosae of rats orally admin- site, and the mucosae from at least two rats (about 2 ng istered dextran sulfate sodium, which induces an enter- of GzmA) were required for detection by binding assay. itis resembling ulcerative colitis (UC), the activity for On the other hand, the activity of GzmA can be granzyme A, a lymphocyte tryptase, increased at an determined sensitively by hydrolysis of N -benzyloxy- earlier stage than that at which UC markers (growth- L-lysine thiobenzyl ester (BLT), a synthetic substrate for regulated gene product/cytokine-induced neutrophil the enzyme,6,8) which is completely inhibited in the chemoattractant-1 and caspase-3) increased. This sug- presence of a recombinant rat PSTI6) (more than 2 mM) gests involvement of the enzyme in the exacerbation and (Fig. 1A). Therefore, of the hydrolysis of BLT by perpetuation of enteritis. samples from large-intestinal mucosae, hydrolysis in which hydrolysis in the absence of PSTI is subtracted Key words: granzyme A; cytotoxic T-lymphocytes; ul- from hydrolysis in the presence of PSTI should cor- cerative colitis; dextran sulfate sodium; respond to that catalyzed by GzmA. In addition, neither pancreatic secretory trypsin inhibitor the binding between GzmA and 125I-labeled PSTI7) nor BLT hydrolysis by a recombinant rat GzmA was A family of serine proteases termed granzymes are inhibited by soybean trypsin inhibitor (SBTI, type I-S, stored in granules of cytotoxic T-lymphocytes (CTLs) Sigma, St.
    [Show full text]