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Pulmonary Vascular Niche Regulates Macrophage Functional Polarization through Endothelial Jag1
Author(s) -
Xing Junjie,
Dai Zhiyu,
Huang Xiaojia,
Zhao Youyang
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.995.10
Subject(s) - macrophage polarization , lung , ards , m2 macrophage , macrophage , medicine , alveolar macrophage , jag1 , immunology , notch signaling pathway , endothelium , diffuse alveolar damage , pathology , biology , in vitro , receptor , acute respiratory distress , biochemistry
BACKGROUND The pathogenesis of acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) have been well studied. Little is known about the mechanism and treatment for resolution of inflammatory lung injury. Especially the interaction of macrophage and pulmonary endothelium during the course of lung injury and its effect on lung injury resolution. METHODS AND RESULTS Using jagged1 endothelial specific mice, we found that endothelial jagged1 deficiency have faster lung injury recovery than wild type mice in LPS induced lung injury. Adoptive transfer M1 macrophage impaired the repair of lung injury in jagged1 endothelial specific knockout mice. Further study showed that recruited macrophages is more M2‐like during the sepsis induced lung injury recovery phase in Jagged1 specific knockout mice. In vitro experiment we also found that inhibition of jagged1 in lung microvascular endothelial cell reprogramming macrophage to the M2 lineage and macrophage Jag1‐notch activation inhibited macrophage M2 transform. CONCLUSIONS Lung EC Jagged1 mediated macrophage polarization via interaction with Notch signaling. Jag1 deletion in endothelial cell or inhibition of Jag1‐notch signal in macrophage may be the therapeutic target in resolving inflammatory lung injury.