The proinflammatory activity of structurally altered elastic fibers

Shadi Mehraban, George Gu, Shuren Ma, Xingjian Liu, Gerard Turino, Jerome Cantor

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The mechanisms responsible for the increased loss of pulmonary function following acute lung inflammation in chronic obstructive pulmonary disease remain poorly understood. To investigate this process, our laboratory developed a hamster model that uses a single intratracheal instillation of LPS to superimpose an inflammatory response on lungs treated with intratracheal elastase 1 week earlier. Parameters measured at 2 days after LPS included total leukocyte content and percent neutrophils in BAL fluid (BALF), and BALF levels of both total and peptide-free elastin-specific crosslinks, desmosine and isodesmosine (DID). Airspace enlargement, measured by the mean linear intercept method, and relative interstitial elastic fiber surface area were determined at 1 week after LPS. Compared with animals only treated with elastase, those receiving elastase/LPS showed statistically significant increases in mean linear intercept (156.2 vs. 85.5 mm), BALF leukocytes (187 vs. 37.3 3 104 cells), neutrophils (39% vs. 3.4%), and free DID (182% vs. 97% of controls), which exceeded the sum of the individual effects of the two agents. Despite increased elastin breakdown, the elastase/LPS group had significantly greater elastic fiber surface area than controls (49% vs. 26%) owing to fragmentation and splaying of the fibers. Additional experiments showed that the combination of elastin peptides and LPS significantly enhanced their separate effects on BALF neutrophils and BALF DID in vivo and leukocyte chemotaxis in vitro. The results suggest that structural changes in elastic fibers have proinflammatory activity and may contribute to the decline in pulmonary function related to chronic obstructive pulmonary disease exacerbations.

Original languageEnglish
Pages (from-to)699-706
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume63
Issue number5
DOIs
StatePublished - Nov 2020
Externally publishedYes

Keywords

  • Chronic obstructive pulmonary disease
  • Desmosine
  • Elastic fibers
  • Elastin peptides
  • Exacerbation

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