Division of work between lung macrophages depends on mitochondrial membrane potential dictated efferocytosis function during lung injury  

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B500
Abstract ID: 6070

Presenting Author:
Somenath Banerjee , Postdoctoral Fellow at Univ. of Illinois, Chicago

Abstract:

In the lungs alveolar macrophages (AMs) and monocyte-derived interstitial macrophages (Mo-Macs), join hands to maintain lung immunity. Analyzing publicly available datasets, showed AMs are enriched with mitochondrial function, but their significance remains elusive. During development, AMs are generated with GM-CSF. In contrast, Mo-Macs require M-CSF to differentiate from monocytes. Here, we mimic the developmental program by differentiating bone marrow monocytes by GMCSF (G-BMDM) or MCSF (M-BMDM) to understand the role of mitochondrial activity in regulating macrophage functions. We confirmed that G-BMDMs highly express Siglecf, Chil3, Ear2, Egr2, etc. and M-BMDM express C1q, Folr2, and Cx3cr1. G-BMDM and M-BMDM showed similar mitochondrial mass. However, G-BMDM showed higher mitochondrial membrane potential (ΔΨm), which is associated with compromised efferocytosis. These findings were recapitulated in vivo after injury. AMs are poor in Prostaglandin E2 (PGE2) production. We, therefore, assessed if PGE2 is a factor in diversifying ΔΨm. Supplying exogenous PGE2 reduced ΔΨm in G-BMDM to the level of M-BMDM and increased efferocytosis. However, this response was not seen in G-BMDM upon inhibiting EP2 receptor or PKA. Further, supplying PGE2 promotes AM proliferation and reduces airspace neutrophils via PKA activity. These findings indicate that the PGE2-PKA axis stabilizes mitochondrial function in macrophages to promote resolution of lung injury via enhanced efferocytosis.