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.
N1 - Funding Information:
We thank Professor Simon C. Watkins (Center for Biological Imaging, Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA) for expert advice on biological image analysis. This work was supported by a grant from the National Heart, Lung, and Blood Institute (NHLBI) R01HL080926 (Z.Y.P. and J.A.K.). CytoSorb polymer was generously provided by CytoSorbents Inc.
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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U2 - 10.1186/cc13969
DO - 10.1186/cc13969
M3 - Article
C2 - 24992991
AN - SCOPUS:84905918387
SN - 1364-8535
VL - 18
JO - Critical Care
JF - Critical Care
IS - 4
M1 - R141
ER -