CD36/Lyn kinase interactions within macrophages promotes pulmonary fibrosis in response to oxidized phospholipid.

Autor: Kwak D; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, 109 Zina Pitcher Place, BSRB 4061, Ann Arbor, MI, 48109, USA., Bradley PB; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, 109 Zina Pitcher Place, BSRB 4061, Ann Arbor, MI, 48109, USA., Subbotina N; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, 109 Zina Pitcher Place, BSRB 4061, Ann Arbor, MI, 48109, USA., Ling S; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, 109 Zina Pitcher Place, BSRB 4061, Ann Arbor, MI, 48109, USA., Teitz-Tennenbaum S; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, 109 Zina Pitcher Place, BSRB 4061, Ann Arbor, MI, 48109, USA.; Pulmonary Section, Department of Medicine, VA Ann Arbor Health System, Ann Arbor, MI, 48105, USA., Osterholzer JJ; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, 109 Zina Pitcher Place, BSRB 4061, Ann Arbor, MI, 48109, USA.; Pulmonary Section, Department of Medicine, VA Ann Arbor Health System, Ann Arbor, MI, 48105, USA., Sisson TH; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, 109 Zina Pitcher Place, BSRB 4061, Ann Arbor, MI, 48109, USA., Kim KK; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, 109 Zina Pitcher Place, BSRB 4061, Ann Arbor, MI, 48109, USA. kevkim@med.umich.edu.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2023 Dec 14; Vol. 24 (1), pp. 314. Date of Electronic Publication: 2023 Dec 14.
DOI: 10.1186/s12931-023-02629-6
Abstrakt: Recent data from human studies and animal models have established roles for type II alveolar epithelial cell (AEC2) injury/apoptosis and monocyte/macrophage accumulation and activation in progressive lung fibrosis. Although the link between these processes is not well defined, we have previously shown that CD36-mediated uptake of apoptotic AEC2s by lung macrophages is sufficient to drive fibrosis. Importantly, apoptotic AEC2s are rich in oxidized phospholipids (oxPL), and amongst its multiple functions, CD36 serves as a scavenger receptor for oxPL. Recent studies have established a role for oxPLs in alveolar scarring, and we hypothesized that uptake and accrual of oxPL by CD36 would cause a macrophage phenotypic change that promotes fibrosis. To test this hypothesis, we treated wild-type and CD36-null mice with the oxPL derivative oxidized phosphocholine (POVPC) and found that CD36-null mice were protected from oxPL-induced scarring. Compared to WT mice, fewer macrophages accumulated in the lungs of CD36-null animals, and the macrophages exhibited a decreased accumulation of intracellular oxidized lipid. Importantly, the attenuated accrual of oxPL in CD36-null macrophages was associated with diminished expression of the profibrotic mediator, TGFβ. Finally, the pathway linking oxPL uptake and TGFβ expression was found to require CD36-mediated activation of Lyn kinase. Together, these observations elucidate a causal pathway that connects AEC2 injury with lung macrophage activation via CD36-mediated uptake of oxPL and suggest several potential therapeutic targets.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje