Pharmacological inhibition of the CCL2-CCR2 axis fails to reduce inflammation in a rat model of acute lung injury
Camprubí-Rimblas, Marta (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Tantinyà, Neus (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Artigas Raventós, Antoni (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Guillamat-Prats, Raquel (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Universitat Autònoma de Barcelona

Date:	2025
Abstract:	New therapeutic approaches are needed to regulate inflammation and control monocyte recruitment in acute respiratory distress syndrome (ARDS). Excessive monocyte influx into the alveolar space can exacerbate lung damage, worsening patient outcomes. Delaying or reducing monocyte recruitment into the alveoli space after the injury has been proposed as a strategy to balance the inflammatory response and mitigate lung damage. In the present study, we assessed the possible role of the CCL2-CCR2 axis as a therapy for controlling acute lung injury after the initial neutrophil-driven influx. We administered a CCL2-antibody (CCL2-Ab) or a CCR2-antagonist (CCR2-Ant) locally into the lung following lung injury induced by HCl/LPS instillation. Our results show that after 24 h, both treatments transiently reduced monocyte infiltration into the bronchoalveolar space. After 72 h, neither CCL2-Ab nor CCR2-Ant sustained a reduced monocyte infiltration or significantly alleviated alveolar or lung inflammation. CCR2-Ant prevented an increase of alveolar permeability, but neither of both treatments, CCL2-Ab nor CCR2-Ant, improved lung damage or function. Our findings indicate that blocking the CCL2-CCR2 axis to control monocyte trafficking at early stages of lung injury is insufficient to control inflammation or prevent disease progression. These results highlight the complexity of ARDS pathophysiology and suggest that alternative strategies may be required to effectively modulate monocyte-driven lung inflammation.
Grants:	Instituto de Salud Carlos III PI18/00677
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Acute lung injury ; Macrophages ; Monocytes ; Cell recruitment ; Acute respiratory distress syndrome ; Inflammation ; Acute inflammation ; Preclinical research
Published in:	Scientific reports, Vol. 15 (august 2025) , ISSN 2045-2322

DOI: 10.1038/s41598-025-11971-2
PMID: 40858671

12 p, 2.7 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Articles > Research articles
Articles > Published articles