Macrophage Cx43 Is Necessary for Fibroblast Cytosolic Calcium and Lung Fibrosis After Injury

Macrophages are paracrine signalers that regulate tissular responses to injury through interactions with parenchymal cells. Connexin hemichannels have recently been shown to mediate efflux of ATP by macrophages, with resulting cytosolic calcium responses in adjacent cells. Here we report that lung m...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in immunology 2022-05, Vol.13, p.880887
Main Authors: Bhattacharyya, Aritra, Torre, Paola, Yadav, Preeti, Boostanpour, Kaveh, Chen, Tian Y, Tsukui, Tatsuya, Sheppard, Dean, Muramatsu, Rieko, Seed, Robert I, Nishimura, Stephen L, Jung, James B, Tang, Xin-Zi, Allen, Christopher D C, Bhattacharya, Mallar
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Animals
Bleomycin - pharmacology
Calcium - metabolism
calcium imaging
Connexin 43 - genetics
Connexin 43 - metabolism
fibroblast
Fibroblasts - metabolism
Idiopathic Pulmonary Fibrosis - metabolism
Immunology
lung fibrosis
macrophage
Macrophages - metabolism
Mice
Mice, Knockout
P2RX4
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Macrophages are paracrine signalers that regulate tissular responses to injury through interactions with parenchymal cells. Connexin hemichannels have recently been shown to mediate efflux of ATP by macrophages, with resulting cytosolic calcium responses in adjacent cells. Here we report that lung macrophages with deletion of connexin 43 (Mac ) had decreased ATP efflux into the extracellular space and induced a decreased cytosolic calcium response in co-cultured fibroblasts compared to WT macrophages. Furthermore, Mac mice had decreased lung fibrosis after bleomycin-induced injury. Interrogating single cell data for human and mouse, we found that was the most highly expressed ATP receptor and calcium channel in lung fibroblasts and that its expression was increased in the setting of fibrosis. Fibroblast-specific deletion of in mice decreased lung fibrosis and collagen expression in lung fibroblasts in the bleomycin model. Taken together, these studies reveal a Cx43-dependent profibrotic effect of lung macrophages and support development of fibroblast P2rx4 as a therapeutic target for lung fibrosis.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2022.880887