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Updated: Aug 11, 2026

Harvesting Murine Alveolar Macrophages and Evaluating Cellular Activation Induced by Polyanhydride Nanoparticles
Published on: June 8, 2012
Macrophage-Derived LCN2 Promotes Methamphetamine-Induced Pulmonary Hypertension
Jie Zhou1, Zhenzhen Xu1, Dao-Bo Peng2
1Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, P.R. China (J.Z., Z.X., X.L., S.C., K.D., Y.J., C.G., X.P., W.-B.X.).
Background:
Methamphetamine (METH), a novel amphetamine-type psychostimulant, is recognized as a risk factor for pulmonary hypertension (PH). Macrophage activation is a key event in pulmonary vascular remodeling and PH progression, but the specific mechanisms of METH-induced PH (METH-PH) remain unclear.
Methods:
A METH-PH mouse model was constructed using wild-type and Lipocalin 2 (LCN2) knockout (LCN2-/-) mice. The involvement and underlying mechanism of LCN2 in METH-PH formation were explored using a METH-PH mouse model and a coculture system of macrophages and pulmonary artery smooth muscle cells.
Results:
In this study, LCN2 was identified as a key regulator of perivascular inflammation and pulmonary vascular remodeling in PH. In the METH-PH mouse model, LCN2 expression was elevated in macrophages within lung tissues. Compared with wild-type mice, LCN2-/- mice were protected from METH-PH, exhibiting reduced pulmonary vascular remodeling and right ventricular pressure. Mechanistically, LCN2 regulates IL-1β (interleukin-1β) production and secretion through NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome activation. In pulmonary artery smooth muscle cells, macrophage-derived LCN2 upregulates the expression of SLC7A11 (solute carrier family 7 member 11) and GPX4 (glutathione peroxidase 4), thereby reducing reactive oxygen species production and preventing ferroptosis.
Conclusions:
Our data revealed a novel mechanism linking LCN2 to macrophages, inflammatory responses, vascular remodeling, and intercellular interactions, indicating that LCN2 could serve as a therapeutic target for METH-induced PH.
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