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

Peng, ZY and Bishop, JV and Wen, XY and Elder, MM and Zhou, F and Chuasuwan, A and Carter, MJ and Devlin, JE and Kaynar, AM and Singbartl, K and Pike, F and Parker, RS and Clermont, G and Federspiel, WJ and Kellum, JA (2014) Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model. Critical Care, 18 (4). ISSN 1364-8535

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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. © 2014 Peng et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Peng, ZY
Bishop, JV
Wen, XYxiw29@pitt.eduXIW29
Elder, MMmie1@pitt.eduMIE1
Zhou, F
Chuasuwan, A
Carter, MJMelinda.Berkey@pitt.eduMJC2
Devlin, JE
Kaynar, AMkaynar@pitt.eduAMK960000-0001-8847-0450
Singbartl, K
Pike, Ffrp3@pitt.eduFRP3
Parker, RSrparker@pitt.eduRPARKER0000-0002-9913-4847
Clermont, Gcler@pitt.eduCLER0000-0002-0163-1379
Federspiel, WJfederspielwj@pitt.eduWFEDERSP0000-0002-7068-6779
Kellum, JAkellum@pitt.eduKELLUM0000-0003-1995-2653
Centers: Other Centers, Institutes, Offices, or Units > Center for Biologic Imaging
Other Centers, Institutes, Offices, or Units > McGowan Institute for Regenerative Medicine
Date: 3 June 2014
Date Type: Publication
Journal or Publication Title: Critical Care
Volume: 18
Number: 4
DOI or Unique Handle: 10.1186/cc13969
Schools and Programs: School of Medicine > Cell Biology and Molecular Physiology
School of Medicine > Critical Care Medicine
Swanson School of Engineering > Bioengineering
Swanson School of Engineering > Chemical and Petroleum Engineering
Refereed: Yes
ISSN: 1364-8535
Date Deposited: 19 Dec 2016 20:19
Last Modified: 16 Feb 2021 14:55


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