Related Experiment Video
Updated: Nov 17, 2025
Alveolar Macrophage Phagocytosis and Bacteria Clearance in Mice
Published on: March 2, 2019
CCR5 signaling promotes lipopolysaccharide-induced macrophage recruitment and alveolar developmental arrest
Ze Chen1, Xiaohua Xie1, Na Jiang1
1Department of Neonatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kong Jiang Road, 200092, Shanghai, China.
Abstract:
The pathogenesis of bronchopulmonary dysplasia (BPD), involves inflammatory, mechanisms that are not fully characterized. Here we report that overexpression of C-C chemokine receptor 5 (CCR5) and its ligands is associated with BPD development. Lipopolysaccharide-induced BPD rats have increased CCR5 and interleukin-1β (IL-1β) levels, and decreased alveolarization, while CCR5 or IL-1β receptor antagonist treatments decreased inflammation and increased alveolarization. CCR5 enhances macrophage migration, macrophage infiltration in the lungs, IL-1β levels, lysyl oxidase activity, and alveolar development arrest. CCR5 expression on monocytes, and its ligands in blood samples from BPD infants, are elevated. Furthermore, batyl alcohol supplementation reduced CCR5 expression and IL-1β production in lipopolysaccharide-exposed rat lungs. Moreover, receptor-interacting kinase 3 (RIP3) upstream regulator of CCR5-cultured RIP3-/- macrophages exhibited partly blocked lipopolysaccharide-induced CCR5 expression. We conclude that increased CCR5 expression is a key mechanism in BPD development and represents a novel therapeutic target for treatment.
Insights
C-C chemokine receptor 5 (CCR5) is linked to bronchopulmonary dysplasia (BPD) development. Targeting CCR5 and its inflammatory pathways may offer new treatments for BPD, improving lung alveolarization.
Area of Science:
- Pulmonary Medicine
- Inflammation Research
- Neonatology
Background:
- Bronchopulmonary dysplasia (BPD) pathogenesis involves complex inflammatory mechanisms.
- The precise role of specific chemokine receptors in BPD remains incompletely understood.
Purpose of the Study:
- To investigate the association between C-C chemokine receptor 5 (CCR5) and its ligands in the development of BPD.
- To explore CCR5 as a potential therapeutic target for BPD.
Main Methods:
- Utilized a lipopolysaccharide (LPS)-induced rat model of BPD.
- Measured CCR5 and interleukin-1β (IL-1β) levels, macrophage activity, and alveolarization.
- Administered CCR5 or IL-1β receptor antagonists and batyl alcohol.
- Analyzed CCR5 expression in monocytes from BPD infants.
- Investigated the role of receptor-interacting kinase 3 (RIP3) in CCR5 regulation.
Main Results:
- LPS-induced BPD rats showed increased CCR5 and IL-1β levels, reduced alveolarization, and enhanced macrophage infiltration.
- CCR5 blockade or IL-1β antagonism improved lung inflammation and alveolar development.
- Elevated CCR5 expression and ligands were found in BPD infants' blood and monocytes.
- Batyl alcohol reduced CCR5 and IL-1β in LPS-exposed rat lungs.
- RIP3 deficiency partially inhibited LPS-induced CCR5 expression.
Conclusions:
- Increased CCR5 expression is a critical factor in BPD pathogenesis.
- CCR5 signaling contributes to lung inflammation, macrophage recruitment, and impaired alveolar development.
- CCR5 represents a promising novel therapeutic target for BPD treatment.
