CRP Enhances the Innate Killing Mechanisms Phagocytosis and ROS Formation in a Conformation and Complement-Dependent Manner

CRP Enhances the Innate Killing Mechanisms Phagocytosis and ROS Formation in a Conformation and Complement-Dependent Manner

Phagocytosis and the formation of reactive oxygen species (ROS) in phagocytic leukocytes are an effective killing mechanism of the innate host defense. These cellular processes of innate immunity function in a complex interplay with humoral factors. C-reactive protein (CRP) in its activated, monomer...

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Main Authors: Johannes Zeller, Balázs Bogner, Jurij Kiefer, David Braig, Oscar Winninger, Mark Fricke, Ebru Karasu, Karlheinz Peter, Markus Huber-Lang, Steffen Ulrich Eisenhardt
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-08-01
Series:Frontiers in Immunology
Subjects:
innate immunity
host defense
C-reactive protein
reactive oxygen species
complement system
complement inhibition
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.721887/full
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spelling doaj-7f5ab2bcdea94288a56e58e482d72bbe2021-08-10T06:23:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-08-011210.3389/fimmu.2021.721887721887CRP Enhances the Innate Killing Mechanisms Phagocytosis and ROS Formation in a Conformation and Complement-Dependent MannerJohannes Zeller0Balázs Bogner1Jurij Kiefer2David Braig3David Braig4Oscar Winninger5Mark Fricke6Ebru Karasu7Karlheinz Peter8Karlheinz Peter9Markus Huber-Lang10Steffen Ulrich Eisenhardt11Department of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, GermanyDepartment of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, GermanyDepartment of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, GermanyDepartment of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, GermanyDivision of Hand, Plastic and Aesthetic Surgery, University Hospital, Ludwig Maximilian University of Munich (LMU), Munich, GermanyDepartment of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, GermanyDepartment of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, GermanyInstitute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, GermanyAtherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, AustraliaDepartment of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, AustraliaInstitute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, GermanyDepartment of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, GermanyPhagocytosis and the formation of reactive oxygen species (ROS) in phagocytic leukocytes are an effective killing mechanism of the innate host defense. These cellular processes of innate immunity function in a complex interplay with humoral factors. C-reactive protein (CRP) in its activated, monomeric isoform (mCRP) has been shown to activate immune cells via the classical complement pathway. We investigated the complement-dependent effects of monomeric CRP (mCRP) on neutrophils and monocyte subtypes using complement-specific inhibitors by both flow cytometry and confocal fluorescence microscopy. We demonstrate that CRP-induced ROS generation is a conformation-specific and complement-dependent process in leukocyte subsets with classical monocytes as the primary source of ROS amongst human monocyte subsets. Elucidation of this complex interplay of CRP and complement in inflammation pathophysiology might help to improve anti-inflammatory therapeutic strategies.https://www.frontiersin.org/articles/10.3389/fimmu.2021.721887/fullinnate immunityhost defenseC-reactive proteinreactive oxygen speciescomplement systemcomplement inhibition
collection DOAJ
language English
format Article
sources DOAJ
author Johannes Zeller
Balázs Bogner
Jurij Kiefer
David Braig
David Braig
Oscar Winninger
Mark Fricke
Ebru Karasu
Karlheinz Peter
Karlheinz Peter
Markus Huber-Lang
Steffen Ulrich Eisenhardt
spellingShingle Johannes Zeller
Balázs Bogner
Jurij Kiefer
David Braig
David Braig
Oscar Winninger
Mark Fricke
Ebru Karasu
Karlheinz Peter
Karlheinz Peter
Markus Huber-Lang
Steffen Ulrich Eisenhardt
CRP Enhances the Innate Killing Mechanisms Phagocytosis and ROS Formation in a Conformation and Complement-Dependent Manner
Frontiers in Immunology
innate immunity
host defense
C-reactive protein
reactive oxygen species
complement system
complement inhibition
author_facet Johannes Zeller
Balázs Bogner
Jurij Kiefer
David Braig
David Braig
Oscar Winninger
Mark Fricke
Ebru Karasu
Karlheinz Peter
Karlheinz Peter
Markus Huber-Lang
Steffen Ulrich Eisenhardt
author_sort Johannes Zeller
title CRP Enhances the Innate Killing Mechanisms Phagocytosis and ROS Formation in a Conformation and Complement-Dependent Manner
title_short CRP Enhances the Innate Killing Mechanisms Phagocytosis and ROS Formation in a Conformation and Complement-Dependent Manner
title_full CRP Enhances the Innate Killing Mechanisms Phagocytosis and ROS Formation in a Conformation and Complement-Dependent Manner
title_fullStr CRP Enhances the Innate Killing Mechanisms Phagocytosis and ROS Formation in a Conformation and Complement-Dependent Manner
title_full_unstemmed CRP Enhances the Innate Killing Mechanisms Phagocytosis and ROS Formation in a Conformation and Complement-Dependent Manner
title_sort crp enhances the innate killing mechanisms phagocytosis and ros formation in a conformation and complement-dependent manner
publisher Frontiers Media S.A.
series Frontiers in Immunology
issn 1664-3224
publishDate 2021-08-01
description Phagocytosis and the formation of reactive oxygen species (ROS) in phagocytic leukocytes are an effective killing mechanism of the innate host defense. These cellular processes of innate immunity function in a complex interplay with humoral factors. C-reactive protein (CRP) in its activated, monomeric isoform (mCRP) has been shown to activate immune cells via the classical complement pathway. We investigated the complement-dependent effects of monomeric CRP (mCRP) on neutrophils and monocyte subtypes using complement-specific inhibitors by both flow cytometry and confocal fluorescence microscopy. We demonstrate that CRP-induced ROS generation is a conformation-specific and complement-dependent process in leukocyte subsets with classical monocytes as the primary source of ROS amongst human monocyte subsets. Elucidation of this complex interplay of CRP and complement in inflammation pathophysiology might help to improve anti-inflammatory therapeutic strategies.
topic innate immunity
host defense
C-reactive protein
reactive oxygen species
complement system
complement inhibition
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.721887/full
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