The relationship between elastin cross linking and alveolar wall rupture in human pulmonary emphysema

Michael Fagiola, Sandra Reznik, Muhammad Riaz, Yibing Qyang, Seoyeon Lee, Joseph Avella, Gerard Turino, Jerome Cantor

Research output: Contribution to journalArticlepeer-review

Abstract

To better define the role of mechanical forces in pulmonary emphysema, we employed methods recently developed in our laboratory to identify microscopic level relationships between airspace size and elastin-specific desmosine and isodesmosine (DID) cross links in normal and emphysematous human lungs. Free DID in wet tissue (a biomarker for elastin degradation) and total DID in formalin-fixed, paraffin-embedded (FFPE) tissue sections were measured using liquid chromatography-tandem mass spectrometry and correlated with alveolar diameter, as determined by the mean linear intercept (MLI) method. There was a positive correlation between free lung DID and MLI (P < 0.0001) in formalin-fixed lungs, and elastin breakdown was greatly accelerated when airspace diameter exceeded 400 μm. In FFPE tissue, DID density was markedly increased beyond 300 μm (P < 0.0001) and leveled off around 400 μm. Elastic fiber surface area similarly peaked at around 400 μm, but to a much lesser extent than DID density, indicating that elastin cross linking is markedly increased in response to early changes in airspace size. These findings support the hypothesis that airspace enlargement is an emergent phenomenon in which initial proliferation of DID cross links to counteract alveolar wall distention is followed by a phase transition involving rapid acceleration of elastin breakdown, alveolar wall rupture, and progression to an active disease state that is less amenable to therapeutic intervention.

Original languageEnglish
Pages (from-to)L747-L755
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume324
Issue number6
DOIs
StatePublished - Jun 2023
Externally publishedYes

Keywords

  • COPD
  • desmosine
  • elastin
  • mass spectrometry
  • pulmonary emphysema

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