Polymorphonuclear Cell Chemotaxis and Suicidal NETosis: Simultaneous Observation Using fMLP, PMA, H7, and Live Cell Imaging

Chemotaxis and the formation of suicidal neutrophil extracellular traps (suicidal NETosis) are key functions of polymorphonuclear cells (PMNs). Neutrophil extracellular traps in particular are known to be significantly involved in the severity of inflammatory and immunological disorders such as rheu...

Full description

Saved in:
Bibliographic Details
Main Authors: Delou Pai, Michael Gruber, Sophie-Marie Pfaehler, Andre Bredthauer, Karla Lehle, Benedikt Trabold
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2020/1415947
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850218773367226368
author Delou Pai
Michael Gruber
Sophie-Marie Pfaehler
Andre Bredthauer
Karla Lehle
Benedikt Trabold
author_facet Delou Pai
Michael Gruber
Sophie-Marie Pfaehler
Andre Bredthauer
Karla Lehle
Benedikt Trabold
author_sort Delou Pai
collection DOAJ
description Chemotaxis and the formation of suicidal neutrophil extracellular traps (suicidal NETosis) are key functions of polymorphonuclear cells (PMNs). Neutrophil extracellular traps in particular are known to be significantly involved in the severity of inflammatory and immunological disorders such as rheumatoid arthritis and Crohn’s disease. Therefore, detailed knowledge of PMNs is essential for analyzing the mechanisms involved in, and developing new therapies for, such diseases. To date, no standard method to analyze these cell activities has been established. This study used in vitro live cell imaging to simultaneously observe and analyze PMN functions. To demonstrate this, the effects of phorbol-12-myristat-13-acetat (PMA, 0.1-10 nM), N-formylmethionine-leucyl-phenylalanine (fMLP, 10 nM), and protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) on PMN chemotaxis and suicidal NETosis were studied. PMA (1 nM-10 nM) resulted in significant concentration-dependent behavior in chemotaxis and an earlier onset of maximum oxidative burst and NET formation of up to 44%. When adding H7, PMA-triggered PMN functions were reduced, demonstrating that all three functions rely mostly on protein kinase C (PKC) activity, while PKC is not essential for fMLP-induced PMN activity. Thus, the method here described can be used to objectively quantify PMN functions and, especially through the regulation of the PKC pathway, could be useful in further clinical studies of immunological disorders.
format Article
id doaj-art-7a4a940ea61e419db2b19afc8dd40681
institution OA Journals
issn 2314-8861
2314-7156
language English
publishDate 2020-01-01
publisher Wiley
record_format Article
series Journal of Immunology Research
spelling doaj-art-7a4a940ea61e419db2b19afc8dd406812025-08-20T02:07:35ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/14159471415947Polymorphonuclear Cell Chemotaxis and Suicidal NETosis: Simultaneous Observation Using fMLP, PMA, H7, and Live Cell ImagingDelou Pai0Michael Gruber1Sophie-Marie Pfaehler2Andre Bredthauer3Karla Lehle4Benedikt Trabold5Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, GermanyDepartment of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, GermanyDepartment of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, GermanyDepartment of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, GermanyDepartment of Cardiothoracic Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, GermanyDepartment of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, GermanyChemotaxis and the formation of suicidal neutrophil extracellular traps (suicidal NETosis) are key functions of polymorphonuclear cells (PMNs). Neutrophil extracellular traps in particular are known to be significantly involved in the severity of inflammatory and immunological disorders such as rheumatoid arthritis and Crohn’s disease. Therefore, detailed knowledge of PMNs is essential for analyzing the mechanisms involved in, and developing new therapies for, such diseases. To date, no standard method to analyze these cell activities has been established. This study used in vitro live cell imaging to simultaneously observe and analyze PMN functions. To demonstrate this, the effects of phorbol-12-myristat-13-acetat (PMA, 0.1-10 nM), N-formylmethionine-leucyl-phenylalanine (fMLP, 10 nM), and protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) on PMN chemotaxis and suicidal NETosis were studied. PMA (1 nM-10 nM) resulted in significant concentration-dependent behavior in chemotaxis and an earlier onset of maximum oxidative burst and NET formation of up to 44%. When adding H7, PMA-triggered PMN functions were reduced, demonstrating that all three functions rely mostly on protein kinase C (PKC) activity, while PKC is not essential for fMLP-induced PMN activity. Thus, the method here described can be used to objectively quantify PMN functions and, especially through the regulation of the PKC pathway, could be useful in further clinical studies of immunological disorders.http://dx.doi.org/10.1155/2020/1415947
spellingShingle Delou Pai
Michael Gruber
Sophie-Marie Pfaehler
Andre Bredthauer
Karla Lehle
Benedikt Trabold
Polymorphonuclear Cell Chemotaxis and Suicidal NETosis: Simultaneous Observation Using fMLP, PMA, H7, and Live Cell Imaging
Journal of Immunology Research
title Polymorphonuclear Cell Chemotaxis and Suicidal NETosis: Simultaneous Observation Using fMLP, PMA, H7, and Live Cell Imaging
title_full Polymorphonuclear Cell Chemotaxis and Suicidal NETosis: Simultaneous Observation Using fMLP, PMA, H7, and Live Cell Imaging
title_fullStr Polymorphonuclear Cell Chemotaxis and Suicidal NETosis: Simultaneous Observation Using fMLP, PMA, H7, and Live Cell Imaging
title_full_unstemmed Polymorphonuclear Cell Chemotaxis and Suicidal NETosis: Simultaneous Observation Using fMLP, PMA, H7, and Live Cell Imaging
title_short Polymorphonuclear Cell Chemotaxis and Suicidal NETosis: Simultaneous Observation Using fMLP, PMA, H7, and Live Cell Imaging
title_sort polymorphonuclear cell chemotaxis and suicidal netosis simultaneous observation using fmlp pma h7 and live cell imaging
url http://dx.doi.org/10.1155/2020/1415947
work_keys_str_mv AT deloupai polymorphonuclearcellchemotaxisandsuicidalnetosissimultaneousobservationusingfmlppmah7andlivecellimaging
AT michaelgruber polymorphonuclearcellchemotaxisandsuicidalnetosissimultaneousobservationusingfmlppmah7andlivecellimaging
AT sophiemariepfaehler polymorphonuclearcellchemotaxisandsuicidalnetosissimultaneousobservationusingfmlppmah7andlivecellimaging
AT andrebredthauer polymorphonuclearcellchemotaxisandsuicidalnetosissimultaneousobservationusingfmlppmah7andlivecellimaging
AT karlalehle polymorphonuclearcellchemotaxisandsuicidalnetosissimultaneousobservationusingfmlppmah7andlivecellimaging
AT benedikttrabold polymorphonuclearcellchemotaxisandsuicidalnetosissimultaneousobservationusingfmlppmah7andlivecellimaging