DOCSLIB.ORG

Markers of Anaphylaxis – a Systematic Review

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Markers of Anaphylaxis – a Systematic Review Advances in Medical Sciences 63 (2018) 265–277 Contents lists available at ScienceDirect Advances in Medical Sciences journal homepage: www.elsevier.com/locate/advms Review article Markers of anaphylaxis – a systematic review a a a Maria Magdalena Tomasiak-Łozowska , Maciej Klimek , Agnieszka Lis , a,b a, Marcin Moniuszko , Anna Bodzenta-Łukaszyk * a Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland b Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland A R T I C L E I N F O A B S T R A C T Article history: fi Received 3 September 2017 Anaphylaxis is de ned as severe, life-threatening, systemic or general, immediate reaction of Accepted 17 December 2017 hypersensitivity, with repeatable symptoms caused by the dose of stimulus which is well tolerated Available online 20 March 2018 by healthy persons. The proper diagnosis, immediate treatment and differential diagnosis are crucial for saving patient's life. However, anaphylaxis is relatively frequently misdiagnosed or confused with other Keywords: clinical entities. Thus, there is a continuous need for identifying detectable markers improving the proper Anaphylaxis diagnosis of anaphylaxis. Here we presented currently known markers of anaphylaxis and discussed in Mast cell more detail the most clinically valuable ones: tryptase, platelet activacting factor (PAF), PAF- Tryptase acethylhydrolase, histamine and its metabolites. Histamine © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved. Platelet activating factor Contents 1. Introduction . 265 2. Material and methods . 266 3. Results and Discussion . 267 3.1. Anaphylaxis – definition, clinical manifestations, differential diagnosis . 267 3.1.1. Role of mast cells in anaphylaxis . 267 3.2. Tryptase . 269 3.3. Histamine . 271 3.3.1. Histamine and myocardial dysfunction . 272 3.4. Platelet-activating factor (PAF) . 273 3.5. Genetic markers of anaphylaxis . 274 4. Conclusion . 274 Conflict of interest . 275 Financial disclosure . 275 References . 275 1. Introduction healthy persons [1]. Mast cells are the most important cells, involved in anaphylactic reactions. The mediators of these cells are: Anaphylaxis is defined as severe, life-threatening, systemic or histamine, tryptase, serotonin, proteoglycans, proteases, chemotac- general, immediate reaction of hypersensitivity, with repeatable tic factors and de novo synthetized lipid mediators: prostaglandin symptoms caused by the dose of stimulus which is well tolerated by D2 (PGD2), leukotriene B4 (LTB4), platelet activacting factor (PAF), cysteinyl leukotrienes (LTC4, LTD4, LTE4,), cytokines (TNF-alpha, IL- 4, IL-5, IL-6, IL-8) [1–4]. Therefore, the proper diagnosis, immediate treatment and also differential diagnosis are crucial for saving * Corresponding author at: Department of Allergology and Internal Diseases, patient’s life. The measurements of potential markers of anaphy- Medical University of Bialystok, M. Sklodowskiej-Curie 24A, 15-276 Bialystok, laxis could be helpful in this situation. Inpresent, the measurements Poland. Tel.: +48 85 831 8373. of tryptase levels are used in clinical practice [1–4]. Scientific E-mail address: [email protected] (A. Bodzenta-Łukaszyk). reports revealed, that the activity of this enzyme, which is https://doi.org/10.1016/j.advms.2017.12.003 1896-1126/© 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved. 266 M.M. Tomasiak-Łozowska et al. / Advances in Medical Sciences 63 (2018) 265–277 characteristic for mast cell granules, correlates well with the PAF was discovered). In January 2017, when we started the severity of anaphylactic reactions [1–4]. The measurements of manuscript preparation, full-text articles were assessed for eligibili- levels of platelet activating factor (which causes the increase in ty. In order to select the data available in the literature, we performed vascular permeability) and PAF-acethylhydrolase, as well as the searching of the data using the following strategy: anaphylaxis À histamine and its metabolites, could be also the valuable tool in 990; anaphylaxis AND clinicaltrialÀ 405; anaphylaxis AND review À cases of anaphylaxis. 2263; anaphylaxis AND case report À 2304; anaphylaxis AND Here we presented currently known markers of anaphylaxis guidelines À 551; mast cell À 19803; mast cell AND anaphylaxis À and discussed in more detail the most clinically valuable ones: 1347; histamine À 21096; histamine AND review À 3610; histamine tryptase, platelet activacting factor (PAF), PAF-acethylhydrolase, AND anaphylaxis À 990; histamine AND clinical trial À 2157; histamine and its metabolites. histamine AND anaphylaxis AND clinical trial À 30; histamine AND anaphylaxis AND case report À 157; histamine receptor À 8551; 2. Material and methods histamine receptor AND anaphylaxis À 202; tryptase À 3132; tryptase AND review À 460; tryptase AND anaphylaxis À 464; A search was started on 01.04.2015. using the MEDLINE/PubMed tryptase AND mast cell À 2570; tryptase AND clinical trial À 128; database (United States National Library of Medicine National tryptase AND case report À 287; PAF À 4046; PAF and review À 347; Institutes of Health). The key words, used in the process of searching PAF AND anaphylaxis À 68; PAF AND clinical trial À 297; PAF AND data; were as follows: anaphylaxis; mast cells; histamine; histamine clinical trial AND anaphylaxis À 0; PAF AND case report AND receptors; tryptase; PAF. In order to select the data available in the anaphylaxis À 0. Filters: published in last 17 years; full text. literature, we performed the searching of the data using the From those full-text articles, 285 were selected for further following strategy: anaphylaxis À 19786; anaphylaxis AND clinical analysis. In the final version of the manuscript, 168 articles were trial À 693; anaphylaxis AND review À 3012; anaphylaxis AND case cited (5 clinical papers, 37 papers on mast cells and their functions report À 4764; anaphylaxis AND guidelinesÀ 576;mast cellÀ 35164; in anaphylaxis, and papers on tryptase, histamine and PAF (n = 31, mast cell AND anaphylaxis À 2418; histamine À 67318; histamine n = 34, n = 61, respectively)). AND review À 8456; histamine AND anaphylaxis À 3474; histamine The search was mainly limited to studies written in English. 166 AND clinical trial À 6330; histamine AND anaphylaxis AND clinical from 168 citations were found in MEDLINE. In the part of the trial À 96; histamine AND anaphylaxis AND case report À 351; manuscript, concerning clinical signs and symptoms, two Polish histamine receptor À 21173; histamine receptor AND anaphylaxis À authors of chapters in textbooks were cited (Refs. [2,55]). Three 535; tryptase À 3990; tryptase AND review À 569; tryptase AND citations, concerning tryptase in diagnostics of allergic diseases, anaphylaxis À 518; tryptase AND mast cell À 3342; tryptase AND anaphylactic reactions to low-molecular weight chemicals, and clinicaltrialÀ 198; tryptaseANDcase reportÀ 366;PAFÀ 10460;PAF idiopathic anaphylaxis, were written in Polish in original versions and review À 830; PAFAND anaphylaxis À 280; PAF AND clinical trial (Refs. [14,17,163], respectively). À 297; PAF AND clinical trial AND anaphylaxis À 0; PAF AND case The process of searching for data is presented graphically report AND anaphylaxis À 0. Filters: published since 1972 (in 1972 according to PRISMA 2009 flow diagram in Fig. 1. Fig. 1. PRISMA 2009 flow diagram [5]. M.M. Tomasiak-Łozowska et al. / Advances in Medical Sciences 63 (2018) 265–277 267 Table 1 3. Results and Discussion Frequency of occurrence of clinical features of anaphylaxis [3,4, modified]. – fi 3.1. Anaphylaxis de nition, clinical manifestations, differential Skin/mucosa Urticarial eruption diagnosis 80–90% Angioedema -oropharyngeal -laryngeal The European Academy of Allergy and Clinical Immunology -intestinal (EAACI) describes anaphylaxis as a severe, life-threatening, Flushing systemic or generalized, immediate hypersensitivity reaction. It Pruritus (palms/soles/oral/genitalia) Bronchopulmonary Laryngeal edema is, in other words, a manifestation of objective, repeatable 60–70% Wheeze/Cough symptoms caused by an exposure to a stimulus of a strength that Rhinitis would be well tolerated by healthy individuals [1]. Cardiac Hypotension/shock fi Anaphylaxis is not usually treated as a speci c disease, but as a 40–50% Reduced cardiac output set of symptoms characterizing a specific reaction of people who Myocardial ischemia Hypotension/shock are hypersensitive to various factors [2]. In the International Reduced cardiac output Statistical Classification of Diseases and Related Health Problems Myocardial ischemia ICD-10, it most closely matches an anaphylactic shock (T78.2). Arrhytmia Clinical manifestations of anaphylaxis depend on the organs or Cardiac arrest Substernal pain systems affected. The clinical symptoms of hypersensitivity Kounis syndrome reactions, defined as anaphylaxis, can have a mild course and be Gastrointestinal Nausea of a local nature (hives, swelling) or give severe reactions with 40–50% Vomiting symptoms of shock (ie. a significant decrease in blood pressure, Diarrhea symptoms of airway obstruction) [2]. Intestinal edema Neurological Dizziness If one of the following criteria is fulfilled, the characteristic <15% Confusion symptoms are very likely to be described as anaphylaxis [3]: Headache Feeling of impending doom 1 Respiratory reactions (shortness of breath, wheezing, stridor,
Load more

Recommended publications
  • Mechanisms Governing Anaphylaxis: Inflammatory Cells, Mediators
    International Journal of Molecular Sciences Review Mechanisms Governing Anaphylaxis: Inflammatory Cells, Mediators, Endothelial Gap Junctions and Beyond Samantha Minh Thy Nguyen 1, Chase Preston Rupprecht 2, Aaisha Haque 3, Debendra Pattanaik 4, Joseph Yusin 5 and Guha Krishnaswamy 1,3,* 1 Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27106, USA; [email protected] 2 The Rowan School of Osteopathic Medicine, Stratford, NJ 08084, USA; [email protected] 3 The Bill Hefner VA Medical Center, Salisbury, NC 27106, USA; [email protected] 4 Division of Allergy and Immunology, UT Memphis College of Medicine, Memphis, TN 38103, USA; [email protected] 5 The Division of Allergy and Immunology, Greater Los Angeles VA Medical Center, Los Angeles, CA 90011, USA; [email protected] * Correspondence: [email protected] Abstract: Anaphylaxis is a severe, acute, life-threatening multisystem allergic reaction resulting from the release of a plethora of mediators from mast cells culminating in serious respiratory, cardiovascular and mucocutaneous manifestations that can be fatal. Medications, foods, latex, exercise, hormones (progesterone), and clonal mast cell disorders may be responsible. More recently, novel syndromes such as delayed reactions to red meat and hereditary alpha tryptasemia have been described. Anaphylaxis manifests as sudden onset urticaria, pruritus, flushing, erythema, Citation: Nguyen, S.M.T.; Rupprecht, angioedema (lips, tongue, airways, periphery), myocardial dysfunction (hypovolemia, distributive
    [Show full text]
  • Supplementary Table 2 Gene Sets Used in GSEA
    Supplementary Table 2 Gene sets used in GSEA Up in RNAi and Sign Confirmed in Inducible Gene Probe Set ID Accession Symbol Gene Title 200660_at NM_005620 S100A11 S100 calcium binding protein A11 (calgizzarin) 200785_s_at NM_002332 LRP1 low density lipoprotein-related protein 1 (alpha-2-macroglobulin receptor) 201325_s_at NM_001423 EMP1 epithelial membrane protein 1 201373_at NM_000445 PLEC1 plectin 1, intermediate filament binding protein 500kDa 201466_s_at NM_002228 JUN v-jun sarcoma virus 17 oncogene homolog (avian) 201952_at AA156721 ALCAM activated leukocyte cell adhesion molecule 202042_at NM_002109 HARS histidyl-tRNA synthetase 202074_s_at NM_021980 OPTN optineurin 202087_s_at NM_001912 CTSL cathepsin L 202588_at NM_000476 AK1 adenylate kinase 1 202609_at NM_004447 EPS8 epidermal growth factor receptor pathway substrate 8 202733_at NM_004199 P4HA2 procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide II 202756_s_at NM_002081 GPC1 glypican 1 202786_at NM_013233 STK39 serine threonine kinase 39 (STE20/SPS1 homolog, yeast) 202859_x_at NM_000584 IL8 interleukin 8 203083_at NM_003247 THBS2 thrombospondin 2 203186_s_at NM_002961 S100A4 S100 calcium binding protein A4 (calcium protein, calvasculin, metastasin, murine placental homolog) 203232_s_at NM_000332 ATXN1 ataxin 1 203233_at NM_000418 IL4R interleukin 4 receptor 203771_s_at AA740186 BLVRA biliverdin reductase A 203821_at NM_001945 HBEGF heparin-binding EGF-like growth factor 203939_at NM_002526 NT5E 5'-nucleotidase, ecto (CD73) 203955_at NM_014811
    [Show full text]
  • Analysis of the Indacaterol-Regulated Transcriptome in Human Airway
    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/04/13/jpet.118.249292.DC1 1521-0103/366/1/220–236$35.00 https://doi.org/10.1124/jpet.118.249292 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:220–236, July 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Analysis of the Indacaterol-Regulated Transcriptome in Human Airway Epithelial Cells Implicates Gene Expression Changes in the s Adverse and Therapeutic Effects of b2-Adrenoceptor Agonists Dong Yan, Omar Hamed, Taruna Joshi,1 Mahmoud M. Mostafa, Kyla C. Jamieson, Radhika Joshi, Robert Newton, and Mark A. Giembycz Departments of Physiology and Pharmacology (D.Y., O.H., T.J., K.C.J., R.J., M.A.G.) and Cell Biology and Anatomy (M.M.M., R.N.), Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Received March 22, 2018; accepted April 11, 2018 Downloaded from ABSTRACT The contribution of gene expression changes to the adverse and activity, and positive regulation of neutrophil chemotaxis. The therapeutic effects of b2-adrenoceptor agonists in asthma was general enriched GO term extracellular space was also associ- investigated using human airway epithelial cells as a therapeu- ated with indacaterol-induced genes, and many of those, in- tically relevant target. Operational model-fitting established that cluding CRISPLD2, DMBT1, GAS1, and SOCS3, have putative jpet.aspetjournals.org the long-acting b2-adrenoceptor agonists (LABA) indacaterol, anti-inflammatory, antibacterial, and/or antiviral activity. Numer- salmeterol, formoterol, and picumeterol were full agonists on ous indacaterol-regulated genes were also induced or repressed BEAS-2B cells transfected with a cAMP-response element in BEAS-2B cells and human primary bronchial epithelial cells by reporter but differed in efficacy (indacaterol $ formoterol .
    [Show full text]
  • 1 No. Affymetrix ID Gene Symbol Genedescription Gotermsbp Q Value 1. 209351 at KRT14 Keratin 14 Structural Constituent of Cyto
    1 Affymetrix Gene Q No. GeneDescription GOTermsBP ID Symbol value structural constituent of cytoskeleton, intermediate 1. 209351_at KRT14 keratin 14 filament, epidermis development <0.01 biological process unknown, S100 calcium binding calcium ion binding, cellular 2. 204268_at S100A2 protein A2 component unknown <0.01 regulation of progression through cell cycle, extracellular space, cytoplasm, cell proliferation, protein kinase C inhibitor activity, protein domain specific 3. 33323_r_at SFN stratifin/14-3-3σ binding <0.01 regulation of progression through cell cycle, extracellular space, cytoplasm, cell proliferation, protein kinase C inhibitor activity, protein domain specific 4. 33322_i_at SFN stratifin/14-3-3σ binding <0.01 structural constituent of cytoskeleton, intermediate 5. 201820_at KRT5 keratin 5 filament, epidermis development <0.01 structural constituent of cytoskeleton, intermediate 6. 209125_at KRT6A keratin 6A filament, ectoderm development <0.01 regulation of progression through cell cycle, extracellular space, cytoplasm, cell proliferation, protein kinase C inhibitor activity, protein domain specific 7. 209260_at SFN stratifin/14-3-3σ binding <0.01 structural constituent of cytoskeleton, intermediate 8. 213680_at KRT6B keratin 6B filament, ectoderm development <0.01 receptor activity, cytosol, integral to plasma membrane, cell surface receptor linked signal transduction, sensory perception, tumor-associated calcium visual perception, cell 9. 202286_s_at TACSTD2 signal transducer 2 proliferation, membrane <0.01 structural constituent of cytoskeleton, cytoskeleton, intermediate filament, cell-cell adherens junction, epidermis 10. 200606_at DSP desmoplakin development <0.01 lectin, galactoside- sugar binding, extracellular binding, soluble, 7 space, nucleus, apoptosis, 11. 206400_at LGALS7 (galectin 7) heterophilic cell adhesion <0.01 2 S100 calcium binding calcium ion binding, epidermis 12. 205916_at S100A7 protein A7 (psoriasin 1) development <0.01 S100 calcium binding protein A8 (calgranulin calcium ion binding, extracellular 13.
    [Show full text]
  • Transcriptomic Analysis Delineates Potential Signature Genes And
    www.nature.com/scientificreports OPEN Transcriptomic analysis delineates potential signature genes and miRNAs associated with the pathogenesis of asthma Prithvi Singh1,5, Archana Sharma2,5, Rishabh Jha1, Shweta Arora2, Rafq Ahmad3, Arshad Husain Rahmani4, Saleh A. Almatroodi4, Ravins Dohare1* & Mansoor Ali Syed2* Asthma is a multifarious disease afecting several million people around the world. It has a heterogeneous risk architecture inclusive of both genetic and environmental factors. This heterogeneity can be utilised to identify diferentially expressed biomarkers of the disease, which may ultimately aid in the development of more localized and molecularly targeted therapies. In this respect, our study complies with meta-analysis of microarray datasets containing mRNA expression profles of both asthmatic and control patients, to identify the critical Diferentially Expressed Genes (DEGs) involved in the pathogenesis of asthma. We found a total of 30 DEGs out of which 13 were involved in the pathway and functional enrichment analysis. Moreover, 5 DEGs were identifed as the hub genes by network centrality-based analysis. Most hub genes were involved in protease/ antiprotease pathways. Also, 26 miRNAs and 20 TFs having an association with these hub genes were found to be intricated in a 3-node miRNA Feed-Forward Loop. Out of these, miR-34b and miR- 449c were identifed as the key miRNAs regulating the expression of SERPINB2 gene and SMAD4 transcription factor. Thus, our study is suggestive of certain miRNAs and unexplored pathways which may pave a way to unravel critical therapeutic targets in asthma. Despite recent advances in anti-asthmatic therapeutics, asthma is still a major global health concern.
    [Show full text]
  • Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis
    International Journal of Molecular Sciences Review Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis Boguslaw Nedoszytko 1,* , Michel Arock 2,3 , Jonathan J. Lyons 4, Guillaume Bachelot 2, Lawrence B. Schwartz 5, Andreas Reiter 6, Mohamad Jawhar 6 , Juliana Schwaab 6 , Magdalena Lange 1, Georg Greiner 7,8,9 , Gregor Hoermann 8,10 , Marek Niedoszytko 11, Dean D. Metcalfe 4 and Peter Valent 8,12 1 Department of Dermatology, Allergology and Venereology, Medical University of Gdansk, 80-211 Gdansk, Poland; [email protected] 2 Department of Hematology, APHP, Hôpital Pitié-Salpêtrière and Sorbonne University, 75013 Paris, France; [email protected] (M.A.); [email protected] (G.B.) 3 Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Cell Death and Drug Resistance in Hematological Disorders Team, 75006 Paris, France 4 Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-188, USA; [email protected] (J.J.L.); [email protected] (D.D.M.) 5 Department of Internal Medicine, Division of Rheumatology, Allergy & Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA; [email protected] 6 University Hospital Mannheim, Heidelberg University, 68167 Mannheim, Germany; [email protected] (A.R.); [email protected] (M.J.); [email protected] (J.S.) 7 Department of Laboratory Medicine, Medical
    [Show full text]
  • Molecular Mechanisms Underlying Toxicant Effects on Mast Cell Signaling and Mitochondria Juyoung Katherine Shim University of Maine, [email protected]
    The University of Maine DigitalCommons@UMaine Electronic Theses and Dissertations Fogler Library Summer 8-17-2018 Molecular Mechanisms Underlying Toxicant Effects on Mast Cell Signaling and Mitochondria Juyoung Katherine Shim University of Maine, [email protected] Follow this and additional works at: https://digitalcommons.library.umaine.edu/etd Part of the Molecular Biology Commons, and the Toxicology Commons Recommended Citation Shim, Juyoung Katherine, "Molecular Mechanisms Underlying Toxicant Effects on Mast Cell Signaling and Mitochondria" (2018). Electronic Theses and Dissertations. 2909. https://digitalcommons.library.umaine.edu/etd/2909 This Open-Access Thesis is brought to you for free and open access by DigitalCommons@UMaine. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of DigitalCommons@UMaine. For more information, please contact [email protected]. MOLECULAR MECHANISMS UNDERLYING TOXICANT EFFECTS ON MAST CELL SIGNALING AND MITOCHONDRIA By Juyoung K. Shim B.A. Hankook University of Foreign Studies, 1994 B.S. Bates College, 2005 A DISSERTATION Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy (in Biochemistry and Molecular Biology) The Graduate School The University of Maine August 2018 Advisory Committee: Julie A. Gosse, Associate Professor of Biochemistry; Advisor John T. Singer, Professor of Microbiology Paul J. Millard, Associate Professor of Chemical and Biological Engineering Rebecca J. Van Beneden, Professor of Biochemistry and Marine Sciences, Director for School of Marine Sciences Robert E. Gundersen, Chair of Molecular and Biomedical Sciences © 2018 Juyoung Katherine Shim All Rights Reserved ii MOLECULAR MECHANISMS UNDERLYING TOXICANT EFFECTS ON MAST CELL SIGNALING AND MITOCHONDRIA By Juyoung K.
    [Show full text]
  • The Emerging Role of Mast Cell Proteases in Asthma
    REVIEW ASTHMA The emerging role of mast cell proteases in asthma Gunnar Pejler1,2 Affiliations: 1Dept of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. 2Dept of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden. Correspondence: Gunnar Pejler, Dept of Medical Biochemistry and Microbiology, BMC, Uppsala University, Box 582, 75123 Uppsala, Sweden. E-mail: [email protected] @ERSpublications Mast cells express large amounts of proteases, including tryptase, chymase and carboxypeptidase A3. An extensive review of how these proteases impact on asthma shows that they can have both protective and detrimental functions. http://bit.ly/2Gu1Qp2 Cite this article as: Pejler G. The emerging role of mast cell proteases in asthma. Eur Respir J 2019; 54: 1900685 [https://doi.org/10.1183/13993003.00685-2019]. ABSTRACT It is now well established that mast cells (MCs) play a crucial role in asthma. This is supported by multiple lines of evidence, including both clinical studies and studies on MC-deficient mice. However, there is still only limited knowledge of the exact effector mechanism(s) by which MCs influence asthma pathology. MCs contain large amounts of secretory granules, which are filled with a variety of bioactive compounds including histamine, cytokines, lysosomal hydrolases, serglycin proteoglycans and a number of MC-restricted proteases. When MCs are activated, e.g. in response to IgE receptor cross- linking, the contents of their granules are released to the exterior and can cause a massive inflammatory reaction. The MC-restricted proteases include tryptases, chymases and carboxypeptidase A3, and these are expressed and stored at remarkably high levels.
    [Show full text]
  • Mast Cell Secretory Granules: Armed for Battle
    REVIEWS Mast cell secretory granules: armed for battle Sara Wernersson and Gunnar Pejler Abstract | Mast cells are important effector cells of the immune system and recent studies show that they have immunomodulatory roles in diverse processes in both health and disease. Mast cells are distinguished by their high content of electron-dense secretory granules, which are filled with large amounts of preformed and pre-activated immunomodulatory compounds. When appropriately activated, mast cells undergo degranulation, a process by which these preformed granule compounds are rapidly released into the surroundings. In many cases, the effects that mast cells have on an immune response are closely associated with the biological actions of the granule compounds that they release, as exemplified by the recent studies showing that mast cell granule proteases account for many of the protective and detrimental effects of mast cells in various inflammatory settings. In this Review, we discuss the current knowledge of mast cell secretory granules. Tr y p ta s e s Mast cells are haematopoietic cells that arise from pluri- The secretory granules of mast cells are filled with a 1–3 Serine proteases that have potent precursors of the bone marrow . After egression large panel of preformed compounds (TABLE 1). When trypsin-like cleavage from the bone marrow, mast cell progenitors circu- mast cells are activated to degranulate, these com- specificities — that is, they late in the blood before they enter various tissues and pounds are released into the extracellular environment cleave peptide bonds on the develop into mature mast cells under the influence of and can have a marked effect on any physiological or carboxy-terminal side of arginine or lysine residues.
    [Show full text]
  • Engineered Type 1 Regulatory T Cells Designed for Clinical Use Kill Primary
    ARTICLE Acute Myeloid Leukemia Engineered type 1 regulatory T cells designed Ferrata Storti Foundation for clinical use kill primary pediatric acute myeloid leukemia cells Brandon Cieniewicz,1* Molly Javier Uyeda,1,2* Ping (Pauline) Chen,1 Ece Canan Sayitoglu,1 Jeffrey Mao-Hwa Liu,1 Grazia Andolfi,3 Katharine Greenthal,1 Alice Bertaina,1,4 Silvia Gregori,3 Rosa Bacchetta,1,4 Norman James Lacayo,1 Alma-Martina Cepika1,4# and Maria Grazia Roncarolo1,2,4# Haematologica 2021 Volume 106(10):2588-2597 1Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 2Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 3San Raffaele Telethon Institute for Gene Therapy, Milan, Italy and 4Center for Definitive and Curative Medicine, Stanford School of Medicine, Stanford, CA, USA *BC and MJU contributed equally as co-first authors #AMC and MGR contributed equally as co-senior authors ABSTRACT ype 1 regulatory (Tr1) T cells induced by enforced expression of interleukin-10 (LV-10) are being developed as a novel treatment for Tchemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft-versus-host disease while mediating graft-versus-leukemia effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML are different on a genetic and epigenetic level, we investigate herein whether LV-10 cells also efficiently kill pAML cells. We show that the majority of primary pAML are killed by LV-10 cells, with different levels of sensitivity to killing. Transcriptionally, pAML sensitive to LV-10 killing expressed a myeloid maturation signature.
    [Show full text]
  • TPSAB1 Monoclonal Antibody (AA1)
    Website: thermofisher.com Lot Number: SB2348992 Customer Service(US): 1 800 955 6288 ext. 1 Technical Support (US): 1 800 955 6288 ext. 441 thermofisher.com/contactus TPSAB1 Monoclonal Antibody (AA1) Catalog Number:MA5-11711 Product Data Sheet Details Species Reactivity Size 500 µL Canine, Feline, Human, Tested species reactivity Non-human primate Host / Isotype Mouse / IgG1 Published Species Reactivity Human, Mouse, Rat Class Monoclonal Type Antibody Tested Applications Dilution * Clone AA1 Western Blot (WB) 1:50 Human mast cell tryptase Immunohistochemistry (Paraffin) Immunogen 1:2000 purified from human lung tissues (IHC (P)) Form Liquid Published Applications Concentration 50µg/ml Immunocytochemistry (ICC) See 1 publications below Purification Protein G Immunohistochemistry (IHC) See 16 publications below Storage Buffer PBS, pH 7.4, with 0.2% BSA * Suggested working dilutions are given as a guide only. It is recommended that the user titrate the product for use in their own experiment using appropriate negative and positive controls. Contains 0.09% sodium azide Storage Conditions 4° C Product Specific Information MA5-11711 targets Mast Cell Tryptase in IHC (P) and WB applications and shows reactivity with Canine, Feline, Human, and Non-human primate samples. The MA5-11711 immunogen is human mast cell tryptase purified from human lung tissues. Background/Target Information Mast cells contain a number of preformed chemical mediators such as histamine, chymase, carboxypeptidase and proteolytic tryptase. A substantial quantity of tryptase is estimated to be found in mast cells of skin and lung and suggestes this enzyme plays a major role in mast cell mediated events. In vitro studies indicate tryptase can cleave C3 to form C3a anaphylatoxin, inactivate fibrinogen as a coaguable substrate for thrombin and activate latent collagenase.
    [Show full text]
  • Download Guide
    Understanding your results This test is used to determine alpha tryptase copy number. Alpha tryptase is encoded by the TPSAB1 gene which is on chromosome 16. The primary gene products of this gene are β-tryptase, which can be produced by TPSAB1 and TPSB2, and α-tryptase, which is only produced by the TPSAB1 gene. Individuals who inherited one copy of α-tryptase–encoding sequence on both have normal serum tryptase levels. This test measures both α- and β-tryptase. A normal result is any combination of α- and β-tryptase that adds up to 4. A positive result – which means there is a duplication or triplication of α-trypase – is a combination of α- and β-tryptase that is 5 or higher. An explanation of the results are included below, however there may be other copy number changes in these genes that have not yet been described. In addition, the assay cannot distinguish between the possible 4,2 genotypes without testing of additional family members. NORMAL RESULT: Alpha-tryptase copy number 2; beta-tryptase copy number 2 TPSB2 TPSAB1 β α β α NORMAL RESULT: Alpha-tryptase copy number 1; beta-tryptase copy number 3 TPSB2 TPSAB1 β β β α 1445 N. Loop W., Suite 820, Houston, TX 77008 (713)868-1438 CLIA#45D1102202 CAP#7212851 NORMAL RESULT: Alpha-tryptase copy number 0; beta-tryptase copy number 4 TPSB2 TPSAB1 β β β β POSITIVE RESULT: Alpha-tryptase copy number 2; beta-tryptase copy number 3 TPSB2 TPSAB1 β α α β β POSITIVE RESULT: Alpha-tryptase copy number 3; beta-tryptase copy number 2 TPSB2 TPSAB1 β α α β α 1445 N.
    [Show full text]