Related Experiment Video

Updated: Jun 17, 2026

Isolation of Lung Retinoid-Containing Cells by Cell Sorting
07:47

Isolation of Lung Retinoid-Containing Cells by Cell Sorting

Published on: April 11, 2025

Targeted PPAR{gamma} deficiency in alveolar macrophages disrupts surfactant catabolism

Anna D Baker1, Anagha Malur, Barbara P Barna

  • 1Department of Internal Medicine, East Carolina University, Greenville, NC, USA.

Journal of Lipid Research
|January 13, 2010
PubMed

Insights

Granulocyte-macrophage colony-stimulating factor (GM-CSF) deficiency causes surfactant buildup in lungs. PPARgamma regulates ABCG1, a key transporter, to maintain lung surfactant homeostasis.

Area of Science:

  • Pulmonary Medicine
  • Cell Biology
  • Lipid Metabolism

Background:

  • Surfactant accumulation in alveolar macrophages is observed in pulmonary alveolar proteinosis (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) knockout (KO) mice.
  • Alveolar macrophages in these conditions are deficient in peroxisome proliferator-activated receptor-gamma (PPARgamma) and the lipid transporter ABCG1.
  • GM-CSF is known to induce PPARgamma, suggesting a potential regulatory pathway.

Purpose of the Study:

  • To investigate the hypothesis that PPARgamma promotes surfactant catabolism by regulating ABCG1.
  • To elucidate the role of PPARgamma in maintaining surfactant homeostasis within alveolar macrophages.

Main Methods:

  • Utilized macrophage-specific PPARgamma (MacPPARgamma) knockout mice.
  • Analyzed lipid content in alveolar macrophages and bronchoalveolar lavage (BAL) fluids.
  • Assessed the expression of ABCG1 and evaluated ABCG1-mediated cholesterol efflux.
  • Examined the expression of liver X receptor (LXR)-ABCA1 pathway components.

Main Results:

  • MacPPARgamma KO mice exhibited foamy, lipid-engorged alveolar macrophages.
  • Significant increases in cholesterol and phospholipid content were found in MacPPARgamma KO alveolar macrophages and BAL fluids.
  • Decreased ABCG1 expression and impaired ABCG1-mediated cholesterol efflux were observed in MacPPARgamma KO alveolar macrophages.
  • Elevated ABCA1 and LXRbeta expression suggested that the LXR-ABCA1 pathway was insufficient to prevent surfactant accumulation.

Conclusions:

  • PPARgamma plays a critical role in regulating surfactant homeostasis in the lungs.
  • PPARgamma mediates this role through the regulation of the lipid transporter ABCG1.
  • The LXR-ABCA1 pathway is not sufficient to compensate for the loss of PPARgamma-mediated surfactant catabolism.

More Related Videos

Alveolar Macrophage Phagocytosis and Bacteria Clearance in Mice11:20

Alveolar Macrophage Phagocytosis and Bacteria Clearance in Mice

Published on: March 2, 2019

In Vivo Assessment of Alveolar Macrophage Efferocytosis Following Ozone Exposure08:54

In Vivo Assessment of Alveolar Macrophage Efferocytosis Following Ozone Exposure

Published on: October 22, 2019

Related Concept Videos

Breathing01:05

Breathing

The process of breathing, inhaling and exhaling, involves the coordinated movement of the chest wall, the lungs, and the muscles that move them. Two muscle groups with important roles in breathing are the diaphragm, located directly below the lungs, and the intercostal muscles, which lie between the ribs. When the diaphragm contracts, it moves downward, increasing the volume of the thoracic cavity and creating more room for the lungs to expand. When the intercostal muscles contract, the ribs...
Chronic Obstructive Pulmonary Disease II: Emphysema01:23

Chronic Obstructive Pulmonary Disease II: Emphysema

Emphysema, a major phenotype of chronic obstructive pulmonary disease (COPD), is characterized by irreversible destruction of alveolar walls and permanent enlargement of distal airspaces. Unlike chronic bronchitis, which primarily affects the airways, emphysema predominantly involves the lung parenchyma, where structural damage leads to airflow limitation.PathophysiologyIt most commonly results from prolonged exposure to cigarette smoke and other toxic gases, particularly cigarette smoke.
Chronic Obstructive Pulmonary Disease-II: Pathophysiology01:20

Chronic Obstructive Pulmonary Disease-II: Pathophysiology

Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation
Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features01:24

Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features

Chronic bronchitis is a key phenotype of chronic obstructive pulmonary disease (COPD), characterized by airway-centered inflammation and mucus overproduction. It develops from long-term exposure to harmful particles or gases, most commonly cigarette smoke, which triggers a persistent inflammatory response.Cellular and Structural ChangesInflammation initially affects the large bronchi and later the smaller airways, with infiltration by immune cells, including neutrophils, macrophages, and...