| First Author | Koganesawa M | Year | 2024 |
| Journal | Immunology | PubMed ID | 38361249 |
| Mgi Jnum | J:345929 | Mgi Id | MGI:7610125 |
| Doi | 10.1111/imm.13766 | Citation | Koganesawa M, et al. (2024) Pla2g5 contributes to viral-like-induced lung inflammation through macrophage proliferation and LA/Ffar1 lung cell recruitment. Immunology |
| abstractText | Macrophages expressing group V phospholipase A(2) (Pla2g5) release the free fatty acid (FFA) linoleic acid (LA), potentiating lung type 2 inflammation. Although Pla2g5 and LA increase in viral infections, their role remains obscure. We generated Pla2g5(flox/flox) mice, deleted Pla2g5 by using the Cx3cr1(cre) transgene, and activated bone marrow-derived macrophages (BM-Macs) with poly:IC, a synthetic double-stranded RNA that triggers a viral-like immune response, known Pla2g5-dependent stimuli (IL-4, LPS + IFNgamma, IL-33 + IL-4 + GM-CSF) and poly:IC + LA followed by lipidomic and transcriptomic analysis. Poly:IC-activated Pla2g5(flox/flox) ;Cx3cr1(cre/+) BM-Macs had downregulation of major bioactive lipids and critical enzymes producing those bioactive lipids. In addition, AKT phosphorylation was lower in poly:IC-stimulated Pla2g5(flox/flox) ;Cx3cr1(cre/+) BM-Macs, which was not restored by adding LA to poly:IC-stimulated BM-Macs. Consistently, Pla2g5(flox/flox) ;Cx3cr1(cre/+) mice had diminished poly:IC-induced lung inflammation, including inflammatory macrophage proliferation, while challenging Pla2g5(flox/flox) ;Cx3cr1(cre/+) mice with poly:IC + LA partially restored lung inflammation and inflammatory macrophage proliferation. Finally, mice lacking FFA receptor-1 (Ffar1)-null mice had reduced poly:IC-induced lung cell recruitment and tissue macrophage proliferation, not corrected by LA. Thus, Pla2g5 contributes to poly:IC-induced lung inflammation by regulating inflammatory macrophage proliferation and LA/Ffar1-mediated lung cell recruitment and tissue macrophage proliferation. |
