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Optical Determination of Age‐Related Changes in Subpleural Collagen of Live Human Lungs
Author(s) -
Islam Mohammad Naimul,
Jin Guangchun,
Bhattacharya Sunita,
Bhattacharya Jahar
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02782
Subject(s) - alveolar wall , lung , pathology , fibrosis , parenchyma , medicine , pulmonary surfactant , lesion , perfusion , chemistry , biochemistry
The impact of age on lung physiology is not known. Collagen is an important determinant of lung structure and function. Therefore, age‐related changes in collagen quantity, geometry and structure can lead to changes in lung function. CT scans of asymptomatic patients reveal age‐dependent increase of subpleural radiologic densities, called interstitial lung abnormalities (ILAs) that predispose to pulmonary fibrosis. However it is not known whether ILAs are collagen deposits that impair alveolar function. Since real‐time fluorescence microscopy (RFI) of the human lung has not been done, we carried out two‐photon and confocal microscopy (2P‐CF) of live, transplant‐reject lungs to determine the age‐related profile of subpleural collagen density (SCD) and whether this affects surfactant secretion. For RFI, we cannulated the bronchus and the artery of the lingular lobe to enable inflation and perfusion. Then, we held the lobe at constant alveolar pressure of 5 cmH2O. To stain alveolar epithelial cells, we subpleurally injected fluorescent dyes by means of a 31‐gauge needle. We detected subpleural collagen as the fluorescence of second harmonics generation (SHG). We quantified subpleural collagen density (SCD) as the integrated collagen fluorescence occurring in the space between the visceral pleura and the alveolar epithelium. To determine surfactant secretion, we quantified the timed appearance of lipid‐sensitive fluorescence in the alveolar space following a transient hyperinflation of the lingular lobe. Our data show that subpleural collagen was evident as well‐defined and evenly spaced cables in young lungs (median age 37 years). By contrast, subpleural collagen in aged lungs (median age 63 years) was marked by poorly formed cables surrounded by diffuse SHG fluorescence. We show that SCDs varied in different regions in all lungs and that SCD was significantly higher in aged than young lungs. Further, in high SCD regions, hyperinflation‐induced alveolar expansion and surfactant secretion were abrogated (p<0.05). Thus, SCDs increase with age and negatively regulate surfactant secretion from adjacent alveoli. SCDs may correspond to ILAs. Our findings raise the novel possibility that a risk‐factor in development of pulmonary fibrosis might be the disruption of alveolar homeostasis caused by age‐related changes in subpleural collagen (HL145547, HL36024). Support or Funding Information HL145547, HL36024