Related Experiment Video
Updated: Dec 18, 2025
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Inflammatory macrophage memory in nonsteroidal anti-inflammatory drug-exacerbated respiratory disease
Pascal Haimerl1, Ulrike Bernhardt2, Sonja Schindela1
1Center of Allergy and Environment, Technical University of Munich and Helmholtz Zentrum München, Munich, Germany.
Background:
Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is a chronic inflammatory condition, which is driven by an aberrant arachidonic acid metabolism. Macrophages are major producers of arachidonic acid metabolites and subject to metabolic reprogramming, but they have been neglected in N-ERD.
Objective:
This study sought to elucidate a potential metabolic and epigenetic macrophage reprogramming in N-ERD.
Methods:
Transcriptional, metabolic, and lipid mediator profiles in macrophages from patients with N-ERD and healthy controls were assessed by RNA sequencing, Seahorse assays, and LC-MS/MS. Metabolites in nasal lining fluid, sputum, and plasma from patients with N-ERD (n = 15) and healthy individuals (n = 10) were quantified by targeted metabolomics analyses. Genome-wide methylomics were deployed to define epigenetic mechanisms of macrophage reprogramming in N-ERD.
Results:
This study shows that N-ERD monocytes/macrophages exhibit an overall reduction in DNA methylation, aberrant metabolic profiles, and an increased expression of chemokines, indicative of a persistent proinflammatory activation. Differentially methylated regions in N-ERD macrophages included genes involved in chemokine signaling and acylcarnitine metabolism. Acylcarnitines were increased in macrophages, sputum, nasal lining fluid, and plasma of patients with N-ERD. On inflammatory challenge, N-ERD macrophages produced increased levels of acylcarnitines, proinflammatory arachidonic acid metabolites, cytokines, and chemokines as compared to healthy macrophages.
Conclusions:
Together, these findings decipher a proinflammatory metabolic and epigenetic reprogramming of macrophages in N-ERD.
Insights
Macrophages in nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) show epigenetic and metabolic changes. These reprogrammed macrophages contribute to the persistent inflammation seen in N-ERD.
Area of Science:
- Immunology
- Metabolomics
- Epigenetics
Background:
- Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is a chronic inflammatory condition driven by abnormal arachidonic acid metabolism.
- Macrophages play a key role in arachidonic acid metabolism but have been understudied in N-ERD.
Purpose of the Study:
- To investigate metabolic and epigenetic reprogramming of macrophages in N-ERD patients.
- To understand the role of these reprogrammed macrophages in N-ERD pathogenesis.
Main Methods:
- Assessed transcriptional, metabolic, and lipid mediator profiles of N-ERD patient macrophages using RNA sequencing and Seahorse assays.
- Quantified metabolites in patient biofluids (nasal lining fluid, sputum, plasma) via targeted metabolomics.
- Performed genome-wide methylomics to identify epigenetic alterations in N-ERD macrophages.
Main Results:
- N-ERD macrophages displayed reduced DNA methylation, altered metabolic profiles, and increased chemokine expression, indicating chronic inflammation.
- Key differentially methylated genes were involved in chemokine signaling and acylcarnitine metabolism.
- Acylcarnitines and pro-inflammatory mediators were elevated in N-ERD macrophages and biofluids, with increased production upon inflammatory challenge.
Conclusions:
- Macrophages in N-ERD undergo significant proinflammatory metabolic and epigenetic reprogramming.
- These findings highlight macrophages as a potential therapeutic target for N-ERD.
More Related Videos
08:54In Vivo Assessment of Alveolar Macrophage Efferocytosis Following Ozone Exposure
Published on: October 22, 2019
06:29Adoptive Transfer of IL-33-Stimulated Macrophages into Bleomycin-Induced Mouse Models to Study Their Effect on Idiopathic Pulmonary Fibrosis In Vivo
Published on: May 5, 2023
Related Concept Videos
01:38Inflammation
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
Chronic Inflammation
01:17Drugs Used in Lower Respiratory Disorders: Overview
Bronchodilators, the first step of respiration enhancement, come in various forms, each with its own mechanism...
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
01:26Asthma-II: Pathophysiology and Classification
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
01:25Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...