Cargando…

Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model

INTRODUCTION: Prior work suggests that leukocyte trafficking is determined by local chemokine gradients between the nidus of infection and the plasma. We recently demonstrated that therapeutic apheresis can alter immune mediator concentrations in the plasma, protect against organ injury, and improve...

Descripción completa

Detalles Bibliográficos
Autores principales: Peng, Zhi-Yong, Bishop, Jeffery V, Wen, Xiao-Yan, Elder, Michele M, Zhou, Feihu, Chuasuwan, Anan, Carter, Melinda J, Devlin, Jason E, Kaynar, A Murat, Singbartl, Kai, Pike, Francis, Parker, Robert S, Clermont, Gilles, Federspiel, William J, Kellum, John A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227131/
https://www.ncbi.nlm.nih.gov/pubmed/24992991
http://dx.doi.org/10.1186/cc13969
_version_ 1782343743284707328
author Peng, Zhi-Yong
Bishop, Jeffery V
Wen, Xiao-Yan
Elder, Michele M
Zhou, Feihu
Chuasuwan, Anan
Carter, Melinda J
Devlin, Jason E
Kaynar, A Murat
Singbartl, Kai
Pike, Francis
Parker, Robert S
Clermont, Gilles
Federspiel, William J
Kellum, John A
author_facet Peng, Zhi-Yong
Bishop, Jeffery V
Wen, Xiao-Yan
Elder, Michele M
Zhou, Feihu
Chuasuwan, Anan
Carter, Melinda J
Devlin, Jason E
Kaynar, A Murat
Singbartl, Kai
Pike, Francis
Parker, Robert S
Clermont, Gilles
Federspiel, William J
Kellum, John A
author_sort Peng, Zhi-Yong
collection PubMed
description INTRODUCTION: Prior work suggests that leukocyte trafficking is determined by local chemokine gradients between the nidus of infection and the plasma. We recently demonstrated that therapeutic apheresis can alter immune mediator concentrations in the plasma, protect against organ injury, and improve survival. Here we aimed to determine whether the removal of chemokines from the plasma by apheresis in experimental peritonitis changes chemokine gradients and subsequently enhances leukocyte localization into the infected compartment, and away from healthy tissues. METHODS: In total, 76 male adult Sprague–Dawley rats weighing 400 g to 600 g were included in this study. Eighteen hours after inducing sepsis by cecal ligation and puncture, we randomized these rats to apheresis or sham treatment for 4 hours. Cytokines, chemokines, and leukocyte counts from blood, peritoneal cavity, and lung were measured. In a separate experiment, we labeled neutrophils from septic donor animals and injected them into either apheresis or sham-treated animals. All numeric data with normal distributions were compared with one-way analysis of variance, and numeric data not normally distributed were compared with the Mann–Whitney U test. RESULTS: Apheresis significantly removed plasma cytokines and chemokines, increased peritoneal fluid-to-blood chemokine (C-X-C motif ligand 1, ligand 2, and C-C motif ligand 2) ratios, and decreased bronchoalveolar lavage fluid-to-blood chemokine ratios, resulting in enhanced leukocyte recruitment into the peritoneal cavity and improved bacterial clearance, but decreased recruitment into the lung. Apheresis also reduced myeloperoxidase activity and histologic injury in the lung, liver, and kidney. These Labeled donor neutrophils exhibited decreased localization in the lung when infused into apheresis-treated animals. CONCLUSIONS: Our results support the concept of chemokine gradient control of leukocyte trafficking and demonstrate the efficacy of apheresis to target this mechanism and reduce leukocyte infiltration into the lung.
format Online
Article
Text
id pubmed-4227131
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-42271312014-11-12 Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model Peng, Zhi-Yong Bishop, Jeffery V Wen, Xiao-Yan Elder, Michele M Zhou, Feihu Chuasuwan, Anan Carter, Melinda J Devlin, Jason E Kaynar, A Murat Singbartl, Kai Pike, Francis Parker, Robert S Clermont, Gilles Federspiel, William J Kellum, John A Crit Care Research INTRODUCTION: Prior work suggests that leukocyte trafficking is determined by local chemokine gradients between the nidus of infection and the plasma. We recently demonstrated that therapeutic apheresis can alter immune mediator concentrations in the plasma, protect against organ injury, and improve survival. Here we aimed to determine whether the removal of chemokines from the plasma by apheresis in experimental peritonitis changes chemokine gradients and subsequently enhances leukocyte localization into the infected compartment, and away from healthy tissues. METHODS: In total, 76 male adult Sprague–Dawley rats weighing 400 g to 600 g were included in this study. Eighteen hours after inducing sepsis by cecal ligation and puncture, we randomized these rats to apheresis or sham treatment for 4 hours. Cytokines, chemokines, and leukocyte counts from blood, peritoneal cavity, and lung were measured. In a separate experiment, we labeled neutrophils from septic donor animals and injected them into either apheresis or sham-treated animals. All numeric data with normal distributions were compared with one-way analysis of variance, and numeric data not normally distributed were compared with the Mann–Whitney U test. RESULTS: Apheresis significantly removed plasma cytokines and chemokines, increased peritoneal fluid-to-blood chemokine (C-X-C motif ligand 1, ligand 2, and C-C motif ligand 2) ratios, and decreased bronchoalveolar lavage fluid-to-blood chemokine ratios, resulting in enhanced leukocyte recruitment into the peritoneal cavity and improved bacterial clearance, but decreased recruitment into the lung. Apheresis also reduced myeloperoxidase activity and histologic injury in the lung, liver, and kidney. These Labeled donor neutrophils exhibited decreased localization in the lung when infused into apheresis-treated animals. CONCLUSIONS: Our results support the concept of chemokine gradient control of leukocyte trafficking and demonstrate the efficacy of apheresis to target this mechanism and reduce leukocyte infiltration into the lung. BioMed Central 2014 2014-07-03 /pmc/articles/PMC4227131/ /pubmed/24992991 http://dx.doi.org/10.1186/cc13969 Text en Copyright © 2014 Peng et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Peng, Zhi-Yong
Bishop, Jeffery V
Wen, Xiao-Yan
Elder, Michele M
Zhou, Feihu
Chuasuwan, Anan
Carter, Melinda J
Devlin, Jason E
Kaynar, A Murat
Singbartl, Kai
Pike, Francis
Parker, Robert S
Clermont, Gilles
Federspiel, William J
Kellum, John A
Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model
title Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model
title_full Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model
title_fullStr Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model
title_full_unstemmed Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model
title_short Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model
title_sort modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227131/
https://www.ncbi.nlm.nih.gov/pubmed/24992991
http://dx.doi.org/10.1186/cc13969
work_keys_str_mv AT pengzhiyong modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT bishopjefferyv modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT wenxiaoyan modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT eldermichelem modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT zhoufeihu modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT chuasuwananan modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT cartermelindaj modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT devlinjasone modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT kaynaramurat modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT singbartlkai modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT pikefrancis modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT parkerroberts modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT clermontgilles modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT federspielwilliamj modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel
AT kellumjohna modulationofchemokinegradientsbyapheresisredirectsleukocytetraffickingtodifferentcompartmentsduringsepsisstudiesinaratmodel