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Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging

There is current need for new approaches to assess/measure organ-level immunoreactivity and ensuing dysfunction in systemic inflammatory response syndrome (SIRS) and sepsis, in order to protect or recover organ function. Using a rat model of systemic sterile inflammatory shock (intravenous LPS admin...

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Autores principales: Martinez-Orengo, Neysha, Tahmazian, Sarine, Lai, Jianhao, Wang, Zeping, Sinharay, Sanhita, Schreiber-Stainthorp, William, Basuli, Falguni, Maric, Dragan, Reid, William, Shah, Swati, Hammoud, Dima A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685400/
https://www.ncbi.nlm.nih.gov/pubmed/36439175
http://dx.doi.org/10.3389/fimmu.2022.1010263
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author Martinez-Orengo, Neysha
Tahmazian, Sarine
Lai, Jianhao
Wang, Zeping
Sinharay, Sanhita
Schreiber-Stainthorp, William
Basuli, Falguni
Maric, Dragan
Reid, William
Shah, Swati
Hammoud, Dima A.
author_facet Martinez-Orengo, Neysha
Tahmazian, Sarine
Lai, Jianhao
Wang, Zeping
Sinharay, Sanhita
Schreiber-Stainthorp, William
Basuli, Falguni
Maric, Dragan
Reid, William
Shah, Swati
Hammoud, Dima A.
author_sort Martinez-Orengo, Neysha
collection PubMed
description There is current need for new approaches to assess/measure organ-level immunoreactivity and ensuing dysfunction in systemic inflammatory response syndrome (SIRS) and sepsis, in order to protect or recover organ function. Using a rat model of systemic sterile inflammatory shock (intravenous LPS administration), we performed PET imaging with a translocator protein (TSPO) tracer, [(18)F]DPA-714, as a biomarker for reactive immunoreactive changes in the brain and peripheral organs. In vivo dynamic PET/CT scans showed increased [(18)F]DPA-714 binding in the brain, lungs, liver and bone marrow, 4 hours after LPS injection. Post-LPS mean standard uptake values (SUV(mean)) at equilibrium were significantly higher in those organs compared to baseline. Changes in spleen [(18)F]DPA-714 binding were variable but generally decreased after LPS. SUV(mean) values in all organs, except the spleen, positively correlated with several serum cytokines/chemokines. In vitro measures of TSPO expression and immunofluorescent staining validated the imaging results. Noninvasive molecular imaging with [(18)F]DPA-714 PET in a rat model of systemic sterile inflammatory shock, along with in vitro measures of TSPO expression, showed brain, liver and lung inflammation, spleen monocytic efflux/lymphocytic activation and suggested increased bone marrow hematopoiesis. TSPO PET imaging can potentially be used to quantify SIRS and sepsis-associated organ-level immunoreactivity and assess the effectiveness of therapeutic and preventative approaches for associated organ failures, in vivo.
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spelling pubmed-96854002022-11-25 Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging Martinez-Orengo, Neysha Tahmazian, Sarine Lai, Jianhao Wang, Zeping Sinharay, Sanhita Schreiber-Stainthorp, William Basuli, Falguni Maric, Dragan Reid, William Shah, Swati Hammoud, Dima A. Front Immunol Immunology There is current need for new approaches to assess/measure organ-level immunoreactivity and ensuing dysfunction in systemic inflammatory response syndrome (SIRS) and sepsis, in order to protect or recover organ function. Using a rat model of systemic sterile inflammatory shock (intravenous LPS administration), we performed PET imaging with a translocator protein (TSPO) tracer, [(18)F]DPA-714, as a biomarker for reactive immunoreactive changes in the brain and peripheral organs. In vivo dynamic PET/CT scans showed increased [(18)F]DPA-714 binding in the brain, lungs, liver and bone marrow, 4 hours after LPS injection. Post-LPS mean standard uptake values (SUV(mean)) at equilibrium were significantly higher in those organs compared to baseline. Changes in spleen [(18)F]DPA-714 binding were variable but generally decreased after LPS. SUV(mean) values in all organs, except the spleen, positively correlated with several serum cytokines/chemokines. In vitro measures of TSPO expression and immunofluorescent staining validated the imaging results. Noninvasive molecular imaging with [(18)F]DPA-714 PET in a rat model of systemic sterile inflammatory shock, along with in vitro measures of TSPO expression, showed brain, liver and lung inflammation, spleen monocytic efflux/lymphocytic activation and suggested increased bone marrow hematopoiesis. TSPO PET imaging can potentially be used to quantify SIRS and sepsis-associated organ-level immunoreactivity and assess the effectiveness of therapeutic and preventative approaches for associated organ failures, in vivo. Frontiers Media S.A. 2022-11-10 /pmc/articles/PMC9685400/ /pubmed/36439175 http://dx.doi.org/10.3389/fimmu.2022.1010263 Text en Copyright © 2022 Martinez-Orengo, Tahmazian, Lai, Wang, Sinharay, Schreiber-Stainthorp, Basuli, Maric, Reid, Shah and Hammoud https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Martinez-Orengo, Neysha
Tahmazian, Sarine
Lai, Jianhao
Wang, Zeping
Sinharay, Sanhita
Schreiber-Stainthorp, William
Basuli, Falguni
Maric, Dragan
Reid, William
Shah, Swati
Hammoud, Dima A.
Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging
title Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging
title_full Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging
title_fullStr Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging
title_full_unstemmed Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging
title_short Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging
title_sort assessing organ-level immunoreactivity in a rat model of sepsis using tspo pet imaging
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685400/
https://www.ncbi.nlm.nih.gov/pubmed/36439175
http://dx.doi.org/10.3389/fimmu.2022.1010263
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