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Visualizing Lung Cellular Adaptations during Combined Ozone and LPS Induced Murine Acute Lung Injury
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RAMP1 Signaling Mitigates Acute Lung Injury by Distinctively Regulating Alveolar and Monocyte-Derived Macrophages.

Atsushi Yamashita1,2, Yoshiya Ito1,3, Mayuko Osada1,4

  • 1Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Japan.

International Journal of Molecular Sciences
|September 28, 2024
PubMed
Summary

Receptor activity-modifying protein 1 (RAMP1) signaling helps reduce lung injury in acute respiratory distress syndrome (ARDS). RAMP1 mitigates inflammation by regulating immune cells, offering a potential ARDS treatment target.

Keywords:
RAMP1immunitymacrophagenerveneutrophil

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Area of Science:

  • Immunology
  • Pulmonology
  • Molecular Biology

Background:

  • Acute respiratory distress syndrome (ARDS) involves excessive cytokine release.
  • Receptor activity-modifying protein 1 (RAMP1), part of the calcitonin gene-related peptide (CGRP) receptor, influences cytokine production.

Purpose of the Study:

  • To investigate the role of RAMP1 signaling in lipopolysaccharide (LPS)-induced acute lung injury (ALI).

Main Methods:

  • Utilized wild-type (WT) and RAMP1-deficient (RAMP1-/-) mouse models.
  • Administered LPS to induce lung injury.
  • Performed adoptive transfer of alveolar macrophages (AMs).
  • Analyzed cytokine levels, immune cell infiltration, and gene expression.

Main Results:

  • RAMP1-/- mice showed exacerbated lung injury, higher cytokine levels, and increased neutrophil infiltration after LPS exposure.
  • RAMP1-deficient AMs produced more cytokines in response to LPS compared to WT AMs.
  • RAMP1 deficiency impaired monocyte-derived macrophage (MDM) recruitment and altered their inflammatory and reparative profiles.
  • CGRP administration reduced cytokine production and neutrophil accumulation in WT mice.

Conclusions:

  • RAMP1 signaling plays a protective role in LPS-induced ALI by modulating AM and MDM functions.
  • Targeting RAMP1 represents a potential therapeutic strategy for ARDS treatment.