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Low-dose adrenomedullin-2/intermedin(8-47) reduces pulmonary ischemia/reperfusion injury

Christian Körner1, Tim Kuchenbuch1, Uwe Pfeil2

  • 1Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.

Peptides
|October 8, 2014
PubMed

Insights

Adrenomedullin-2/intermedin(8-47) protects mouse lungs from ischemia/reperfusion injury by preserving the blood-air barrier and reducing leukocyte infiltration. This peptide may offer therapeutic benefits for lung transplantation and cardiopulmonary bypass procedures.

Area of Science:

  • Pulmonary Medicine
  • Vascular Biology
  • Regenerative Medicine

Background:

  • Adrenomedullin-2/intermedin (AM2/INT) is known to stabilize the pulmonary microvascular barrier.
  • Ischemia/reperfusion (I/R) injury is a significant complication in lung transplantation and cardiopulmonary bypass.
  • The protective effects of AM2/INT against lung I/R injury require further investigation.

Purpose of the Study:

  • To test the hypothesis that adrenomedullin-2/intermedin(8-47) protects mouse lungs from ischemia/reperfusion injury in vivo.
  • To evaluate the impact of AM2/INT on the integrity of the blood-air barrier and leukocyte infiltration following lung I/R.

Main Methods:

  • A mouse model of lung ischemia/reperfusion was established using C57BL/6 mice.
  • Mice received intravenous injections of adrenomedullin-2/intermedin(8-47) before clamping and reperfusion.
  • Lung injury was assessed by electron microscopy, stereological methods, and bronchoalveolar lavage to quantify leukocyte infiltration.

Main Results:

  • Ischemia/reperfusion injury led to significant intraalveolar leukocyte accumulation in the ischemic lung.
  • Two doses of adrenomedullin-2/intermedin(8-47) (10ng/kg) dramatically reduced leukocyte infiltration by approximately 85% (p≤0.001).
  • Electron microscopy confirmed that AM2/INT protected the integrity of the blood-air barrier and reduced neutrophil granulocyte infiltration.

Conclusions:

  • Adrenomedullin-2/intermedin(8-47) ameliorates early lung ischemia/reperfusion injury in mice.
  • The protective mechanism involves preserving the blood-air barrier integrity and reducing leukocyte influx.
  • AM2/INT demonstrates potential therapeutic value in clinical scenarios involving lung injury, such as transplantation and cardiopulmonary bypass.
Keywords:
Blood–air barrierBronchoalveolar lavageIntermedinLeukocyteStereology

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