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Isolation and Identification of Extravascular Immune Cells of the Heart
Published on: August 23, 2018
The protective role of GATA6+ pericardial macrophages in pericardial inflammation
David M Hughes1, Taejoon Won2, Monica V Talor2
1Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
Insights
GATA6+ pericardial macrophages prevent pericarditis and reduce inflammatory cell trafficking after myocardial infarction (MI). However, they do not impact myocardial inflammation, fibrosis, or cardiac function post-MI.
Area of Science:
- Immunology
- Cardiology
- Cell Biology
Background:
- Pericardial macrophages, specifically GATA6-expressing ones, have been implicated in post-myocardial infarction (MI) cardiac repair.
- Conflicting literature exists regarding their role in myocardial fibrosis and inflammation following MI.
Purpose of the Study:
- To investigate the specific role of GATA6+ pericardial macrophages in the context of myocardial infarction (MI) and pericarditis.
- To determine their influence on myocardial inflammation, cardiac fibrosis, and cardiac function.
Main Methods:
- Utilized mouse models to study GATA6+ pericardial macrophages.
- Assessed the impact of GATA6+ macrophage absence on IL-33 induced pericarditis, MI, and coxsackievirus-B3 induced myocarditis.
- Performed in vitro stimulation assays comparing GATA6+ macrophages with bone marrow-derived macrophages.
Main Results:
- GATA6+ pericardial macrophages are crucial for preventing IL-33 induced pericarditis and limiting inflammatory cell infiltration into the pericardial cavity post-MI.
- Absence of GATA6+ macrophages did not alter myocardial inflammation, fibrosis, or cardiac function after MI or viral myocarditis.
- In vitro, GATA6+ macrophages exhibit reduced transcriptional activity and do not upregulate inflammatory markers in fibroblasts.
Conclusions:
- GATA6+ pericardial macrophages play a vital role in modulating pericardial inflammation.
- These macrophages do not significantly influence myocardial inflammation or fibrosis development post-MI.
Abstract:
Prior research has suggested that GATA6+ pericardial macrophages may traffic to the myocardium to prevent interstitial fibrosis after myocardial infarction (MI), while subsequent literature claims that they do not. We demonstrate that GATA6+ pericardial macrophages are critical for preventing IL-33 induced pericarditis and attenuate trafficking of inflammatory monocytes and granulocytes to the pericardial cavity after MI. However, absence of GATA6+ macrophages did not affect myocardial inflammation due to MI or coxsackievirus-B3 induced myocarditis, or late-stage cardiac fibrosis and cardiac function post MI. GATA6+ macrophages are significantly less transcriptionally active following stimulation in vitro compared to bone marrow-derived macrophages and do not induce upregulation of inflammatory markers in fibroblasts. This suggests that GATA6+ pericardial macrophages attenuate inflammation through their interactions with surrounding cells. We therefore conclude that GATA6+ pericardial macrophages are critical in modulating pericardial inflammation, but do not play a significant role in controlling myocardial inflammation or fibrosis.
