Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis

Isaac Ginsburg,1 Maya Korem,2 Erez Koren,3 James Varani4 1Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University, Jerusalem, Israel; 2Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 3Research and Deve...

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Autores principales:	Ginsburg I, Korem M, Koren E, Varani J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Synergism tissue damage bacterial toxin bacteriolysis cationic proteins sepsis Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/5a794d118e5140febf0494bcb18887bd
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spelling	oai:doaj.org-article:5a794d118e5140febf0494bcb18887bd2021-12-02T04:33:38ZPro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis1178-7031https://doaj.org/article/5a794d118e5140febf0494bcb18887bd2019-01-01T00:00:00Zhttps://www.dovepress.com/pro-inflammatory-agents-released-by-pathogens-dying-host-cells-and-neu-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Isaac Ginsburg,1 Maya Korem,2 Erez Koren,3 James Varani4 1Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University, Jerusalem, Israel; 2Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 3Research and Development Department, Clexio Biosciences Ltd, Petah Tikva, Israel; 4Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI, USA Abstract: We postulate that the extensive cell and tissue damage inflicted by many infectious, inflammatory and post-inflammatory episodes is an enled result of a synergism among the invading microbial agents, host neutrophils and dead and dying cells in the nidus. Microbial toxins and other metabolites along with the plethora of pro-inflammatory agents released from activated neutrophils massively recruited to the infectious sites and high levels of cationic histones, other cationic peptides, proteinases and Th1 cytokines released from activated polymorphonuclear neutrophils (PMNs) and from necrotized tissues may act in concert (synergism) to bring about cell killing and tissue destruction. Multiple, diverse interactions among the many potential pro-inflammatory moieties have been described in these complex lesions. Such infections are often seen in the skin and aerodigestive tract where the tissue is exposed to the environment, but can occur in any tissue. Commonly, the tissue-destructive infections are caused by group A streptococci, pneumococci, Staphylococcus aureus, meningococci, Escherichia coli and Shigella, although many other microbial species are seen on occasion. All these microbial agents are characterized by their ability to recruit large numbers of PMNs. Given the complex nature of the disease process, it is proposed that, to treat these multifactorial disorders, a “cocktail” of anti-inflammatory agents combined with non-bacteriolytic antibiotics and measures to counteract the critical toxic role of cationic moieties might prove more effective than a strategy based on attacking the bacteria alone. Keywords: synergism, tissue damage, bacterial toxin, bacteriolysis, cationic proteins, sepsisGinsburg IKorem MKoren EVarani JDove Medical PressarticleSynergismtissue damagebacterial toxinbacteriolysiscationic proteinssepsisPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 12, Pp 35-47 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Synergism tissue damage bacterial toxin bacteriolysis cationic proteins sepsis Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	Synergism tissue damage bacterial toxin bacteriolysis cationic proteins sepsis Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Ginsburg I Korem M Koren E Varani J Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis
description	Isaac Ginsburg,1 Maya Korem,2 Erez Koren,3 James Varani4 1Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University, Jerusalem, Israel; 2Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 3Research and Development Department, Clexio Biosciences Ltd, Petah Tikva, Israel; 4Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI, USA Abstract: We postulate that the extensive cell and tissue damage inflicted by many infectious, inflammatory and post-inflammatory episodes is an enled result of a synergism among the invading microbial agents, host neutrophils and dead and dying cells in the nidus. Microbial toxins and other metabolites along with the plethora of pro-inflammatory agents released from activated neutrophils massively recruited to the infectious sites and high levels of cationic histones, other cationic peptides, proteinases and Th1 cytokines released from activated polymorphonuclear neutrophils (PMNs) and from necrotized tissues may act in concert (synergism) to bring about cell killing and tissue destruction. Multiple, diverse interactions among the many potential pro-inflammatory moieties have been described in these complex lesions. Such infections are often seen in the skin and aerodigestive tract where the tissue is exposed to the environment, but can occur in any tissue. Commonly, the tissue-destructive infections are caused by group A streptococci, pneumococci, Staphylococcus aureus, meningococci, Escherichia coli and Shigella, although many other microbial species are seen on occasion. All these microbial agents are characterized by their ability to recruit large numbers of PMNs. Given the complex nature of the disease process, it is proposed that, to treat these multifactorial disorders, a “cocktail” of anti-inflammatory agents combined with non-bacteriolytic antibiotics and measures to counteract the critical toxic role of cationic moieties might prove more effective than a strategy based on attacking the bacteria alone. Keywords: synergism, tissue damage, bacterial toxin, bacteriolysis, cationic proteins, sepsis
format	article
author	Ginsburg I Korem M Koren E Varani J
author_facet	Ginsburg I Korem M Koren E Varani J
author_sort	Ginsburg I
title	Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis
title_short	Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis
title_full	Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis
title_fullStr	Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis
title_full_unstemmed	Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis
title_sort	pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/5a794d118e5140febf0494bcb18887bd
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Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis

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