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Lung epithelial cell-derived C3 protects against pneumonia-induced lung injury

ABSTRACT: The complement component C3 is a fundamental plasma protein for host defense, produced largely by the liver. However, recent work has demonstrated the critical importance of tissue-specific C3 expression in cell survival. Here we analyzed the effects of local versus peripheral sources of C3 expression in a model of bacterial pneumonia. While mice with global C3 deficiency had severe pneumonia-induced lung injury, those deficient in liver-deficient C3 remain protected, comparable to wildtype mice. Human lung transcriptome analysis showed that secretory epithelial cells, such as club cells, are a major source of C3. Mice with a tamoxifen-induced C3 gene ablation from club cells in the lung had worse pulmonary injury compared to similarly treated controls, despite maintaining normal circulating C3 levels. Finally, in human cellular and mouse pneumonia models, we show that C3 reduces epithelial cell death mediated through the alternative pathway component Factor B, rather than the C3aR. Thus, our findings suggest that a locally-derived C3-Factor B pathway protects the lung mucosal barrier.

ORGANISM(S): Homo sapiens

PROVIDER: GSE218554 | GEO | 2023/02/03

REPOSITORIES: GEO

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mRNA profiles of tumor infiltrating macrophage and monocyte derived from C3 wild-type and knock-out mice, subjected to sarcoma transplantable model

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Lung epithelial cell-derived C3 protects against pneumonia-induced lung injury

Project description:Lung epithelial cell-derived C3 protects against pneumonia-induced lung injury

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