Elastin Cables Define the Axial Connective Tissue System in the Murine Lung.
The axial connective tissue system is a fiber continuum of the lung that maintains alveolar surface area during changes in lung volume. Although the molecular anatomy of the axial system remains undefined, the fiber continuum of the lung is central to contemporary models of lung micromechanics and alveolar regeneration. To provide a detailed molecular structure of the axial connective tissue system, we examined the extracellular matrix of murine lungs. The lungs were decellularized using a 24 hr detergent treatment protocol. Systematic evaluation of the decellularized lungs demonstrated no residual cellular debris; morphometry demonstrated a mean 39 ± 7% reduction in lung dimensions. Scanning electron microscopy (SEM) demonstrated an intact structural hierarchy within the decellularized lung. Light, fluorescence, and SEM of precision-cut lung slices demonstrated that alveolar duct structure was defined by a cable line element encased in basement membrane. The cable line element arose in the distal airways, passed through septal tips and inserted into neighboring blood vessels and visceral pleura. The ropelike appearance, collagenase resistance and anti-elastin immunostaining indicated that the cable was an elastin macromolecule. Our results indicate that the helical line element of the axial connective tissue system is composed of an elastin cable that not only defines the structure of the alveolar duct, but also integrates the axial connective tissue system into visceral pleura and peripheral blood vessels.
Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
Willi
W
Wagner
Laboratory of Adaptive and Regenerative Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Robert D
RD
Bennett
Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
Maximilian
M
Ackermann
Laboratory of Adaptive and Regenerative Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Alexandra B
AB
Ysasi
Laboratory of Adaptive and Regenerative Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Janeil
J
Belle
Laboratory of Adaptive and Regenerative Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Cristian D
CD
Valenzuela
Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
Andreas
A
Pabst
Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, Massachusetts.
Akira
A
Tsuda
Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
Moritz A
MA
Konerding
Laboratory of Adaptive and Regenerative Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Steven J
SJ
Mentzer
D000818:Animals; D003238:Connective Tissue / Q000033:anatomy & histology* / Q000378:metabolism / Q000648:ultrastructure; D004549:Elastin / Q000378:metabolism*; D008168:Lung / Q000033:anatomy & histology* / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning
D004549:Elastin
electron microscopy; extracellular matrix; lung; microstructure