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

Zhi Yong Peng, Jeffery V. Bishop, Xiao Yan Wen, Michele M. Elder, Feihu Zhou, Anan Chuasuwan, Melinda J. Carter, Jason E. Devlin, A. M. Kaynar, Kai Singbartl, Francis Pike, Robert S. Parker, Gilles Clermont, William J. Federspiel, John A. Kellum

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numberR141
JournalCritical Care
Volume18
Issue number4
DOIs
StatePublished - Jun 3 2014

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Blood Component Removal
Chemokines
Sepsis
Leukocytes
Lung
Peritoneal Cavity
Chemokine CXCL1
Neutrophils
Cytokines
Ligands
Ascitic Fluid
Normal Distribution
Bronchoalveolar Lavage Fluid
Lung Injury
Nonparametric Statistics
Peritonitis
Leukocyte Count
Punctures
Peroxidase
Ligation

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

Cite this

Peng, Z. Y., Bishop, J. V., Wen, X. Y., Elder, M. M., Zhou, F., Chuasuwan, A., ... Kellum, J. A. (2014). Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model. Critical Care, 18(4), [R141]. https://doi.org/10.1186/cc13969
Peng, Zhi Yong ; Bishop, Jeffery V. ; Wen, Xiao Yan ; Elder, Michele M. ; Zhou, Feihu ; Chuasuwan, Anan ; Carter, Melinda J. ; Devlin, Jason E. ; Kaynar, A. M. ; 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. In: Critical Care. 2014 ; Vol. 18, No. 4.
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title = "Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model",
abstract = "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.",
author = "Peng, {Zhi Yong} and Bishop, {Jeffery V.} and Wen, {Xiao Yan} and Elder, {Michele M.} and Feihu Zhou and Anan Chuasuwan and Carter, {Melinda J.} and Devlin, {Jason E.} and Kaynar, {A. M.} and Kai Singbartl and Francis Pike and Parker, {Robert S.} and Gilles Clermont and Federspiel, {William J.} and Kellum, {John A.}",
year = "2014",
month = "6",
day = "3",
doi = "10.1186/cc13969",
language = "English (US)",
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Peng, ZY, Bishop, JV, Wen, XY, Elder, MM, Zhou, F, Chuasuwan, A, Carter, MJ, Devlin, JE, Kaynar, AM, Singbartl, K, Pike, F, Parker, RS, Clermont, G, Federspiel, WJ & Kellum, JA 2014, 'Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model', Critical Care, vol. 18, no. 4, R141. https://doi.org/10.1186/cc13969

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. M.; Singbartl, Kai; Pike, Francis; Parker, Robert S.; Clermont, Gilles; Federspiel, William J.; Kellum, John A.

In: Critical Care, Vol. 18, No. 4, R141, 03.06.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model

AU - Peng, Zhi Yong

AU - Bishop, Jeffery V.

AU - Wen, Xiao Yan

AU - Elder, Michele M.

AU - Zhou, Feihu

AU - Chuasuwan, Anan

AU - Carter, Melinda J.

AU - Devlin, Jason E.

AU - Kaynar, A. M.

AU - Singbartl, Kai

AU - Pike, Francis

AU - Parker, Robert S.

AU - Clermont, Gilles

AU - Federspiel, William J.

AU - Kellum, John A.

PY - 2014/6/3

Y1 - 2014/6/3

N2 - 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.

AB - 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.

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DO - 10.1186/cc13969

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