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Macrophage–endothelial cell crosstalk orchestrates neutrophil recruitment in inflamed mucosa

Neutrophil (PMN) mobilization to sites of insult is critical for host defense and requires transendothelial migration (TEM). TEM involves several well-studied sequential adhesive interactions with vascular endothelial cells (ECs); however, what initiates or terminates this process is not well-unders...

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Autores principales: Ren, Xingsheng, Manzanares, Laura D., Piccolo, Enzo B., Urbanczyk, Jessica M., Sullivan, David P., Yalom, Lenore K., Bui, Triet M., Lantz, Connor, Najem, Hinda, Dulai, Parambir S., Heimberger, Amy B., Thorp, Edward B., Sumagin, Ronen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10378177/
https://www.ncbi.nlm.nih.gov/pubmed/37261911
http://dx.doi.org/10.1172/JCI170733
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author Ren, Xingsheng
Manzanares, Laura D.
Piccolo, Enzo B.
Urbanczyk, Jessica M.
Sullivan, David P.
Yalom, Lenore K.
Bui, Triet M.
Lantz, Connor
Najem, Hinda
Dulai, Parambir S.
Heimberger, Amy B.
Thorp, Edward B.
Sumagin, Ronen
author_facet Ren, Xingsheng
Manzanares, Laura D.
Piccolo, Enzo B.
Urbanczyk, Jessica M.
Sullivan, David P.
Yalom, Lenore K.
Bui, Triet M.
Lantz, Connor
Najem, Hinda
Dulai, Parambir S.
Heimberger, Amy B.
Thorp, Edward B.
Sumagin, Ronen
author_sort Ren, Xingsheng
collection PubMed
description Neutrophil (PMN) mobilization to sites of insult is critical for host defense and requires transendothelial migration (TEM). TEM involves several well-studied sequential adhesive interactions with vascular endothelial cells (ECs); however, what initiates or terminates this process is not well-understood. Here, we describe what we believe to be a new mechanism where vessel-associated macrophages through localized interactions primed EC responses to form ICAM-1 “hot spots” to support PMN TEM. Using real-time intravital microscopy of LPS-inflamed intestines in CX3CR1-EGFP macrophage-reporter mice, complemented by whole-mount tissue imaging and flow cytometry, we found that macrophage vessel association is critical for the initiation of PMN-EC adhesive interactions, PMN TEM, and subsequent accumulation in the intestinal mucosa. Anti–colony stimulating factor 1 receptor Ab-mediated macrophage depletion in the lamina propria and at the vessel wall resulted in elimination of ICAM-1 hot spots impeding PMN-EC interactions and TEM. Mechanistically, the use of human clinical specimens, TNF-α–KO macrophage chimeras, TNF-α/TNF receptor (TNF-α/TNFR) neutralization, and multicellular macrophage-EC-PMN cocultures revealed that macrophage-derived TNF-α and EC TNFR2 axis mediated this regulatory mechanism and was required for PMN TEM. As such, our findings identified clinically relevant mechanisms by which macrophages regulate PMN trafficking in inflamed mucosa.
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spelling pubmed-103781772023-08-01 Macrophage–endothelial cell crosstalk orchestrates neutrophil recruitment in inflamed mucosa Ren, Xingsheng Manzanares, Laura D. Piccolo, Enzo B. Urbanczyk, Jessica M. Sullivan, David P. Yalom, Lenore K. Bui, Triet M. Lantz, Connor Najem, Hinda Dulai, Parambir S. Heimberger, Amy B. Thorp, Edward B. Sumagin, Ronen J Clin Invest Research Article Neutrophil (PMN) mobilization to sites of insult is critical for host defense and requires transendothelial migration (TEM). TEM involves several well-studied sequential adhesive interactions with vascular endothelial cells (ECs); however, what initiates or terminates this process is not well-understood. Here, we describe what we believe to be a new mechanism where vessel-associated macrophages through localized interactions primed EC responses to form ICAM-1 “hot spots” to support PMN TEM. Using real-time intravital microscopy of LPS-inflamed intestines in CX3CR1-EGFP macrophage-reporter mice, complemented by whole-mount tissue imaging and flow cytometry, we found that macrophage vessel association is critical for the initiation of PMN-EC adhesive interactions, PMN TEM, and subsequent accumulation in the intestinal mucosa. Anti–colony stimulating factor 1 receptor Ab-mediated macrophage depletion in the lamina propria and at the vessel wall resulted in elimination of ICAM-1 hot spots impeding PMN-EC interactions and TEM. Mechanistically, the use of human clinical specimens, TNF-α–KO macrophage chimeras, TNF-α/TNF receptor (TNF-α/TNFR) neutralization, and multicellular macrophage-EC-PMN cocultures revealed that macrophage-derived TNF-α and EC TNFR2 axis mediated this regulatory mechanism and was required for PMN TEM. As such, our findings identified clinically relevant mechanisms by which macrophages regulate PMN trafficking in inflamed mucosa. American Society for Clinical Investigation 2023-08-01 /pmc/articles/PMC10378177/ /pubmed/37261911 http://dx.doi.org/10.1172/JCI170733 Text en © 2023 Ren et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Ren, Xingsheng
Manzanares, Laura D.
Piccolo, Enzo B.
Urbanczyk, Jessica M.
Sullivan, David P.
Yalom, Lenore K.
Bui, Triet M.
Lantz, Connor
Najem, Hinda
Dulai, Parambir S.
Heimberger, Amy B.
Thorp, Edward B.
Sumagin, Ronen
Macrophage–endothelial cell crosstalk orchestrates neutrophil recruitment in inflamed mucosa
title Macrophage–endothelial cell crosstalk orchestrates neutrophil recruitment in inflamed mucosa
title_full Macrophage–endothelial cell crosstalk orchestrates neutrophil recruitment in inflamed mucosa
title_fullStr Macrophage–endothelial cell crosstalk orchestrates neutrophil recruitment in inflamed mucosa
title_full_unstemmed Macrophage–endothelial cell crosstalk orchestrates neutrophil recruitment in inflamed mucosa
title_short Macrophage–endothelial cell crosstalk orchestrates neutrophil recruitment in inflamed mucosa
title_sort macrophage–endothelial cell crosstalk orchestrates neutrophil recruitment in inflamed mucosa
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10378177/
https://www.ncbi.nlm.nih.gov/pubmed/37261911
http://dx.doi.org/10.1172/JCI170733
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