Role of CD11b+ Macrophages in Intraperitoneal Lipopolysaccharide-Induced Aberrant Lymphangiogenesis and Lymphatic Function in the Diaphragm
Identifieur interne : 006046 ( Main/Exploration ); précédent : 006045; suivant : 006047Role of CD11b+ Macrophages in Intraperitoneal Lipopolysaccharide-Induced Aberrant Lymphangiogenesis and Lymphatic Function in the Diaphragm
Auteurs : Kyung Eun Kim ; Young-Jun Koh ; Bong-Hyun Jeon ; Cholsoon Jang ; Jinah Han ; Raghu P. Kataru ; Reto A. Schwendener ; Jin-Man Kim ; Gou Young KohSource :
- The American Journal of Pathology [ 0002-9440 ] ; 2009.
Abstract
Lymphatic vessels in the diaphragm are essential for draining peritoneal fluid, but little is known about their pathological changes during inflammation. Here we characterized diaphragmatic lymphatic vessels in a peritonitis model generated by daily i.p. administration of lipopolysaccharide (LPS) in mice. Intraperitoneal LPS increased lymphatic density, branching, sprouts, connections, and network formation in the diaphragm in time- and dose-dependent manners. These changes were reversible on discontinuation of LPS administration. The LPS-induced lymphatic density and remodeling occur mainly through proliferation of lymphatic endothelial cells. CD11b+ macrophages were massively accumulated and closely associated with the lymphatic vessels changed by i.p. LPS. Both RT-PCR assays and experiments with vascular endothelial growth factor-C/D blockade and macrophage-depletion indicated that the CD11b+ macrophage-derived lymphangiogenic factors vascular endothelial growth factor-C/D could be major mediators of LPS-induced lymphangiogenesis and lymphatic remodeling through paracrine activity. Functional assays with India ink and fluorescein isothiocyanate-microspheres indicated that impaired peritoneal fluid drainage in diaphragm of LPS-induced peritonitis mice was due to inflammatory fibrosis and massive attachment of CD11b+ macrophages on the peritoneal side of the diaphragmatic lymphatic vessels. These findings reveal that CD11b+ macrophages play an important role in i.p. LPS-induced aberrant lymphangiogenesis and lymphatic dysfunction in the diaphragm.
Url:
DOI: 10.2353/ajpath.2009.090133
PubMed: 19762711
PubMed Central: 2751568
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>Lymphatic vessels in the diaphragm are essential for draining peritoneal fluid, but little is known about their pathological changes during inflammation. Here we characterized diaphragmatic lymphatic vessels in a peritonitis model generated by daily i.p. administration of lipopolysaccharide (LPS) in mice. Intraperitoneal LPS increased lymphatic density, branching, sprouts, connections, and network formation in the diaphragm in time- and dose-dependent manners. These changes were reversible on discontinuation of LPS administration. The LPS-induced lymphatic density and remodeling occur mainly through proliferation of lymphatic endothelial cells. CD11b<sup>+</sup>
macrophages were massively accumulated and closely associated with the lymphatic vessels changed by i.p. LPS. Both RT-PCR assays and experiments with vascular endothelial growth factor-C/D blockade and macrophage-depletion indicated that the CD11b<sup>+</sup>
macrophage-derived lymphangiogenic factors vascular endothelial growth factor-C/D could be major mediators of LPS-induced lymphangiogenesis and lymphatic remodeling through paracrine activity. Functional assays with India ink and fluorescein isothiocyanate-microspheres indicated that impaired peritoneal fluid drainage in diaphragm of LPS-induced peritonitis mice was due to inflammatory fibrosis and massive attachment of CD11b<sup>+</sup>
macrophages on the peritoneal side of the diaphragmatic lymphatic vessels. These findings reveal that CD11b<sup>+</sup>
macrophages play an important role in i.p. LPS-induced aberrant lymphangiogenesis and lymphatic dysfunction in the diaphragm.</p>
</div>
</front>
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<name sortKey="Jang, Cholsoon" sort="Jang, Cholsoon" uniqKey="Jang C" first="Cholsoon" last="Jang">Cholsoon Jang</name>
<name sortKey="Jeon, Bong Hyun" sort="Jeon, Bong Hyun" uniqKey="Jeon B" first="Bong-Hyun" last="Jeon">Bong-Hyun Jeon</name>
<name sortKey="Kataru, Raghu P" sort="Kataru, Raghu P" uniqKey="Kataru R" first="Raghu P." last="Kataru">Raghu P. Kataru</name>
<name sortKey="Kim, Jin Man" sort="Kim, Jin Man" uniqKey="Kim J" first="Jin-Man" last="Kim">Jin-Man Kim</name>
<name sortKey="Kim, Kyung Eun" sort="Kim, Kyung Eun" uniqKey="Kim K" first="Kyung Eun" last="Kim">Kyung Eun Kim</name>
<name sortKey="Koh, Gou Young" sort="Koh, Gou Young" uniqKey="Koh G" first="Gou Young" last="Koh">Gou Young Koh</name>
<name sortKey="Koh, Young Jun" sort="Koh, Young Jun" uniqKey="Koh Y" first="Young-Jun" last="Koh">Young-Jun Koh</name>
<name sortKey="Schwendener, Reto A" sort="Schwendener, Reto A" uniqKey="Schwendener R" first="Reto A." last="Schwendener">Reto A. Schwendener</name>
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