Peripheral neutrophil functions and cell signalling in Crohn`s disease.

The role of the innate immunity in the pathogenesis of Crohn's disease (CD), an inflammatory bowel disease, is a subject of increasing interest. Neutrophils (PMN) are key members of the innate immune system which migrate to sites of bacterial infection and initiate the defence against microbes...

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Autores principales:	Rajesh Somasundaram, Veerle J A A Nuij, C Janneke van der Woude, Ernst J Kuipers, Maikel P Peppelenbosch, Gwenny M Fuhler
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8b07e07528a34ca5bc894ae13167c671
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spelling	oai:doaj.org-article:8b07e07528a34ca5bc894ae13167c6712021-11-18T08:41:07ZPeripheral neutrophil functions and cell signalling in Crohn`s disease.1932-620310.1371/journal.pone.0084521https://doaj.org/article/8b07e07528a34ca5bc894ae13167c6712013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24367671/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The role of the innate immunity in the pathogenesis of Crohn's disease (CD), an inflammatory bowel disease, is a subject of increasing interest. Neutrophils (PMN) are key members of the innate immune system which migrate to sites of bacterial infection and initiate the defence against microbes by producing reactive oxygen species (ROS), before undergoing apoptosis. It is believed that impaired innate immune responses contribute to CD, but it is as yet unclear whether intrinsic defects in PMN signal transduction and corresponding function are present in patients with quiescent disease. We isolated peripheral blood PMN from CD patients in remission and healthy controls (HC), and characterised migration, bacterial uptake and killing, ROS production and cell death signalling. Whereas IL8-induced migration and signalling were normal in CD, trans-epithelial migration was significantly impaired. Uptake and killing of E. coli were normal. However, an increased ROS production was observed in CD PMN after stimulation with the bacterial peptide analogue fMLP, which was mirrored by an increased fMLP-triggered ERK and AKT signal activation. Interestingly, cleavage of caspase-3 and caspase-8 during GMCSF-induced rescue from cell-death was decreased in CD neutrophils, but a reduced survival signal emanating from STAT3 and AKT pathways was concomitantly observed, resulting in a similar percentage of end stage apoptotic PMN in CD patients and HC. In toto, these data show a disturbed signal transduction activation and functionality in peripheral blood PMN from patients with quiescent CD, which point toward an intrinsic defect in innate immunity in these patients.Rajesh SomasundaramVeerle J A A NuijC Janneke van der WoudeErnst J KuipersMaikel P PeppelenboschGwenny M FuhlerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e84521 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rajesh Somasundaram Veerle J A A Nuij C Janneke van der Woude Ernst J Kuipers Maikel P Peppelenbosch Gwenny M Fuhler Peripheral neutrophil functions and cell signalling in Crohn`s disease.
description	The role of the innate immunity in the pathogenesis of Crohn's disease (CD), an inflammatory bowel disease, is a subject of increasing interest. Neutrophils (PMN) are key members of the innate immune system which migrate to sites of bacterial infection and initiate the defence against microbes by producing reactive oxygen species (ROS), before undergoing apoptosis. It is believed that impaired innate immune responses contribute to CD, but it is as yet unclear whether intrinsic defects in PMN signal transduction and corresponding function are present in patients with quiescent disease. We isolated peripheral blood PMN from CD patients in remission and healthy controls (HC), and characterised migration, bacterial uptake and killing, ROS production and cell death signalling. Whereas IL8-induced migration and signalling were normal in CD, trans-epithelial migration was significantly impaired. Uptake and killing of E. coli were normal. However, an increased ROS production was observed in CD PMN after stimulation with the bacterial peptide analogue fMLP, which was mirrored by an increased fMLP-triggered ERK and AKT signal activation. Interestingly, cleavage of caspase-3 and caspase-8 during GMCSF-induced rescue from cell-death was decreased in CD neutrophils, but a reduced survival signal emanating from STAT3 and AKT pathways was concomitantly observed, resulting in a similar percentage of end stage apoptotic PMN in CD patients and HC. In toto, these data show a disturbed signal transduction activation and functionality in peripheral blood PMN from patients with quiescent CD, which point toward an intrinsic defect in innate immunity in these patients.
format	article
author	Rajesh Somasundaram Veerle J A A Nuij C Janneke van der Woude Ernst J Kuipers Maikel P Peppelenbosch Gwenny M Fuhler
author_facet	Rajesh Somasundaram Veerle J A A Nuij C Janneke van der Woude Ernst J Kuipers Maikel P Peppelenbosch Gwenny M Fuhler
author_sort	Rajesh Somasundaram
title	Peripheral neutrophil functions and cell signalling in Crohn`s disease.
title_short	Peripheral neutrophil functions and cell signalling in Crohn`s disease.
title_full	Peripheral neutrophil functions and cell signalling in Crohn`s disease.
title_fullStr	Peripheral neutrophil functions and cell signalling in Crohn`s disease.
title_full_unstemmed	Peripheral neutrophil functions and cell signalling in Crohn`s disease.
title_sort	peripheral neutrophil functions and cell signalling in crohn`s disease.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/8b07e07528a34ca5bc894ae13167c671
work_keys_str_mv	AT rajeshsomasundaram peripheralneutrophilfunctionsandcellsignallingincrohnsdisease AT veerlejaanuij peripheralneutrophilfunctionsandcellsignallingincrohnsdisease AT cjannekevanderwoude peripheralneutrophilfunctionsandcellsignallingincrohnsdisease AT ernstjkuipers peripheralneutrophilfunctionsandcellsignallingincrohnsdisease AT maikelppeppelenbosch peripheralneutrophilfunctionsandcellsignallingincrohnsdisease AT gwennymfuhler peripheralneutrophilfunctionsandcellsignallingincrohnsdisease
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Peripheral neutrophil functions and cell signalling in Crohn`s disease.

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