Myeloperoxidase: a front-line defender against phagocytosed microorganisms
Seymour J. Klebanoff,Anthony J. Kettle,Henry Rosen,Christine C. Winterbourn,William M. Nauseef +4 more
TLDR
Evidence is presented in support of MPO as a major arm of oxidative killing by neutrophils and it is proposed that the essential contribution ofMPO to normal innate host defense is manifest only when exposure to pathogens overwhelms the capacity of other host defense mechanisms.Abstract:
Successful immune defense requires integration of multiple effector systems to match the diverse virulence properties that members of the microbial world might express as they initiate and promote infection. Human neutrophils--the first cellular responders to invading microbes--exert most of their antimicrobial activity in phagosomes, specialized membrane-bound intracellular compartments formed by ingestion of microorganisms. The toxins generated de novo by the phagocyte NADPH oxidase and delivered by fusion of neutrophil granules with nascent phagosomes create conditions that kill and degrade ingested microbes. Antimicrobial activity reflects multiple and complex synergies among the phagosomal contents, and optimal action relies on oxidants generated in the presence of MPO. The absence of life-threatening infectious complications in individuals with MPO deficiency is frequently offered as evidence that the MPO oxidant system is ancillary rather than essential for neutrophil-mediated antimicrobial activity. However, that argument fails to consider observations from humans and KO mice that demonstrate that microbial killing by MPO-deficient cells is less efficient than that of normal neutrophils. We present evidence in support of MPO as a major arm of oxidative killing by neutrophils and propose that the essential contribution of MPO to normal innate host defense is manifest only when exposure to pathogens overwhelms the capacity of other host defense mechanisms.read more
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
Andrea Cossarizza,Hyun-Dong Chang,Andreas Radbruch,Andreas Acs,Dieter Adam,Sabine Adam-Klages,William W. Agace,William W. Agace,Nima Aghaeepour,Mübeccel Akdis,Matthieu Allez,Larissa Nogueira Almeida,Giorgia Alvisi,Graham Anderson,Immanuel Andrä,Francesco Annunziato,Achille Anselmo,Petra Bacher,Cosima T. Baldari,Sudipto Bari,Vincenzo Barnaba,Vincenzo Barnaba,Joana Barros-Martins,Luca Battistini,Wolfgang Bauer,Sabine Baumgart,Nicole Baumgarth,Dirk Baumjohann,Bianka Baying,Mary Bebawy,Burkhard Becher,Wolfgang Beisker,Vladimir Benes,Rudi Beyaert,Alfonso Blanco,Dominic A. Boardman,Christian Bogdan,Jessica G. Borger,Giovanna Borsellino,Philip E. Boulais,Jolene Bradford,Dirk Brenner,Dirk Brenner,Ryan R. Brinkman,Anna E. S. Brooks,Dirk H. Busch,Martin Büscher,Timothy P. Bushnell,Federica Calzetti,Garth Cameron,Ilenia Cammarata,Xuetao Cao,Susanna Cardell,Stefano Casola,Marco A. Cassatella,Andrea Cavani,Antonio Celada,Lucienne Chatenoud,Pratip K. Chattopadhyay,Sue Chow,Eleni Christakou,Eleni Christakou,Luka Cicin-Sain,Mario Clerici,Federico Colombo,Laura Cook,Anne Cooke,Andrea M. Cooper,Alexandra J. Corbett,Antonio Cosma,Lorenzo Cosmi,Pierre Coulie,Ana Cumano,Ljiljana Cvetkovic,Van Duc Dang,Chantip Dang-Heine,Martin S. Davey,Derek Davies,Sara De Biasi,Genny Del Zotto,Gelo Victoriano Dela Cruz,Michael Delacher,Silvia Della Bella,Paolo Dellabona,Günnur Deniz,Mark C. Dessing,James P. Di Santo,Andreas Diefenbach,Francesco Dieli,Andreas Dolf,Thomas Dörner,Regine J. Dress,Diana Dudziak,Michael L. Dustin,Charles-Antoine Dutertre,Charles-Antoine Dutertre,Friederike Ebner,Sidonia B G Eckle,Matthias Edinger,Pascale Eede,Götz R. A. Ehrhardt,Marcus Eich,Pablo Engel,Britta Engelhardt,Anna Erdei,Charlotte Esser,Bart Everts,Maximilien Evrard,Christine S. Falk,Todd A. Fehniger,Mar Felipo-Benavent,Helen Ferry,Markus Feuerer,Andrew Filby,Kata Filkor,Simon Fillatreau,Marie Follo,Irmgard Förster,John Bellamy Foster,Gemma A. 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TL;DR: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community providing the theory and key practical aspects offlow cytometry enabling immunologists to avoid the common errors that often undermine immunological data.
Journal ArticleDOI
Neutrophils at work
TL;DR: This Review examines in vivo observations of the recruitment of neutrophils from blood to tissues in models of blood-borne infections versus bacterial invasion through epithelial linings, and examines data on novel aspects of the activation of NADPH oxidase and the heterogeneity of phagosomes.
Journal ArticleDOI
Neutrophils: Between host defence, immune modulation, and tissue injury
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TL;DR: Current understanding of neutrophils in host-pathogen interactions and disease involvement is summarized, illustrating the versatility and plasticity of the neutrophil, moving between host defence, immune modulation, and tissue damage.
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TL;DR: The identity and chemical properties of the specific oxidants produced by neutrophils in different situations are discussed, and what is known about oxidative mechanisms of microbial killing, inflammatory tissue damage, and signaling is discussed.
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Myeloperoxidase: Its role for host defense, inflammation, and neutrophil function
TL;DR: Recent studies using animal models of various inflammatory diseases have demonstrated that MPO deficiency results in the exaggeration of inflammatory response, and that it affects neutrophil functions including cytokine production.
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