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Neutrophil Trafficking in Pulmonary Inflammation: Monitoring Migration and Blockade with 111In-Labeled Leukocytes

Palestro, Christopher J. ; Linge, Helena LU ; Nichols, Kenneth J. ; Ochani, Kanta; Bhargava, Kuldeep K. and Miller, Edmund J (2015) In J Pulm Respir Med 5(5). p.1-5
Abstract (Swedish)
Abstract
Aim: Although imaging of In vitro labeled leukocytes is commonly used for diagnosing inflammation and infection, data concerning the use of this technique to monitor neutrophil trafficking are scarce. Here we investigated the
potential of 111In-in vitro labeled leukocytes (InWBC) to monitor neutrophil trafficking in an animal model of pulmonary inflammation.
Methods: F344 rats were divided into 3 groups: Controls (received only InWBC), Inflammation (intra-tracheally challenged with lipoteichoic acid (LTA)+peptidoglycan (PGN) two hours before InWBC injection), and Blockade
(pulmonary challenge with receptor blockade [LTAPGN+Antileukinate, a CXC receptor 1 and 2 antagonist]). Leukocytes were obtained from donor rats... (More)
Abstract
Aim: Although imaging of In vitro labeled leukocytes is commonly used for diagnosing inflammation and infection, data concerning the use of this technique to monitor neutrophil trafficking are scarce. Here we investigated the
potential of 111In-in vitro labeled leukocytes (InWBC) to monitor neutrophil trafficking in an animal model of pulmonary inflammation.
Methods: F344 rats were divided into 3 groups: Controls (received only InWBC), Inflammation (intra-tracheally challenged with lipoteichoic acid (LTA)+peptidoglycan (PGN) two hours before InWBC injection), and Blockade
(pulmonary challenge with receptor blockade [LTAPGN+Antileukinate, a CXC receptor 1 and 2 antagonist]). Leukocytes were obtained from donor rats and labeled with 111In-oxine using standard procedures. Labeling efficiency
and leukocyte integrity were determined. Animals were administered 3.7-4.6 MBq InWBC via the tail vein, and were imaged 18-30 hours later and then euthanized. Post mortem the lungs were lavaged and total and differential alveolar cell counts performed. Lung tissue myeloperoxidase (MPO) activity was determined. Lung, heart, liver, spleen, kidney, marrow, intestine, blood, and muscle were harvested and organ activity/gm tissue determined. Results: InWBC labeling efficiency and cell integrity were not significantly different among groups. InWBC pulmonary activity was significantly higher (p<0.0001) in the Inflammation group (17.10 ± 2.04%) than in the Controls (1.76 ± 0.60%) and the Blockade group (9.74 ± 1.14%). Hemocytometer assessment of the bronchoalveolar lavage fluid revealed that the total number of neutrophils was significantly higher in the Inflammation group than in Controls and the Blockade group. Pulmonary MPO activity (pg/mg tissue) was significantly higher (p<0.01) in the Inflammation group (14.11 ± 5.56%) than in Controls (5.22 ± 4.77%) and the Blockade group (3.66 ± 3.77%). InWBC splenic activity was significantly higher (p<0.0001) in the Controls than in the Inflammation and Blockade groups. In the remaining organs, InWBC activity was significantly higher in the Blockade group than in the Control and the Inflammation groups.
Conclusions: In a rat model of pulmonary inflammation using Antileukinate to block neutrophil chemokine receptors, InWBC accurately characterized both pulmonary and extrapulmonary neutrophil trafficking. These data indicate that InWBC may be useful to monitor both pulmonary and extrapulmonary neutrophil trafficking associated with lung inflammation and its regulation. (Less)
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published
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in
J Pulm Respir Med
volume
5
issue
5
pages
1 - 5
ISSN
2161-105X
DOI
10.4172/2161-105X.1000289
language
English
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no
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7a0cb613-005b-48be-a02b-bc15c67e0c10
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2017-06-22 12:03:19
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@article{7a0cb613-005b-48be-a02b-bc15c67e0c10,
  abstract     = {Abstract<br>
Aim: Although imaging of In vitro labeled leukocytes is commonly used for diagnosing inflammation and infection, data concerning the use of this technique to monitor neutrophil trafficking are scarce. Here we investigated the<br>
potential of 111In-in vitro labeled leukocytes (InWBC) to monitor neutrophil trafficking in an animal model of pulmonary inflammation.<br>
Methods: F344 rats were divided into 3 groups: Controls (received only InWBC), Inflammation (intra-tracheally challenged with lipoteichoic acid (LTA)+peptidoglycan (PGN) two hours before InWBC injection), and Blockade<br>
(pulmonary challenge with receptor blockade [LTAPGN+Antileukinate, a CXC receptor 1 and 2 antagonist]). Leukocytes were obtained from donor rats and labeled with 111In-oxine using standard procedures. Labeling efficiency<br>
and leukocyte integrity were determined. Animals were administered 3.7-4.6 MBq InWBC via the tail vein, and were imaged 18-30 hours later and then euthanized. Post mortem the lungs were lavaged and total and differential alveolar cell counts performed. Lung tissue myeloperoxidase (MPO) activity was determined. Lung, heart, liver, spleen, kidney, marrow, intestine, blood, and muscle were harvested and organ activity/gm tissue determined. Results: InWBC labeling efficiency and cell integrity were not significantly different among groups. InWBC pulmonary activity was significantly higher (p&lt;0.0001) in the Inflammation group (17.10 ± 2.04%) than in the Controls (1.76 ± 0.60%) and the Blockade group (9.74 ± 1.14%). Hemocytometer assessment of the bronchoalveolar lavage fluid revealed that the total number of neutrophils was significantly higher in the Inflammation group than in Controls and the Blockade group. Pulmonary MPO activity (pg/mg tissue) was significantly higher (p&lt;0.01) in the Inflammation group (14.11 ± 5.56%) than in Controls (5.22 ± 4.77%) and the Blockade group (3.66 ± 3.77%). InWBC splenic activity was significantly higher (p&lt;0.0001) in the Controls than in the Inflammation and Blockade groups. In the remaining organs, InWBC activity was significantly higher in the Blockade group than in the Control and the Inflammation groups.<br>
Conclusions: In a rat model of pulmonary inflammation using Antileukinate to block neutrophil chemokine receptors, InWBC accurately characterized both pulmonary and extrapulmonary neutrophil trafficking. These data indicate that InWBC may be useful to monitor both pulmonary and extrapulmonary neutrophil trafficking associated with lung inflammation and its regulation.},
  author       = {Palestro, Christopher J.  and Linge, Helena and Nichols, Kenneth J.  and Ochani, Kanta and Bhargava, Kuldeep K.  and Miller, Edmund J},
  issn         = {2161-105X},
  language     = {eng},
  number       = {5},
  pages        = {1--5},
  series       = {J Pulm Respir Med},
  title        = {Neutrophil Trafficking in Pulmonary Inflammation: Monitoring Migration and Blockade with 111In-Labeled Leukocytes},
  url          = {http://dx.doi.org/10.4172/2161-105X.1000289},
  volume       = {5},
  year         = {2015},
}