Details

Autor(en) / Beteiligte

• Van Dyken, Steven J.
• Liang, Hong-Erh
• Naikawadi, Ram P.
• Woodruff, Prescott G.
• Wolters, Paul J.
• Erle, David J.
• Locksley, Richard M.

Titel

Spontaneous Chitin Accumulation in Airways and Age-Related Fibrotic Lung Disease

Ist Teil von

• Cell, 2017-04, Vol.169 (3), p.497-509.e13

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The environmentally widespread polysaccharide chitin is degraded and recycled by ubiquitous bacterial and fungal chitinases. Although vertebrates express active chitinases from evolutionarily conserved loci, their role in mammalian physiology is unclear. We show that distinct lung epithelial cells secrete acidic mammalian chitinase (AMCase), which is required for airway chitinase activity. AMCase-deficient mice exhibit premature morbidity and mortality, concomitant with accumulation of environmentally derived chitin polymers in the airways and expression of pro-fibrotic cytokines. Over time, these mice develop spontaneous pulmonary fibrosis, which is ameliorated by restoration of lung chitinase activity by genetic or therapeutic approaches. AMCase-deficient epithelial cells express fibrosis-associated gene sets linked with cell stress pathways. Mice with lung fibrosis due to telomere dysfunction and humans with interstitial lung disease also accumulate excess chitin polymers in their airways. These data suggest that altered chitin clearance could exacerbate fibrogenic pathways in the setting of lung diseases characterized by epithelial cell dysfunction. [Display omitted] •AMCase-expressing epithelial cells mediate endochitinase activity in the airways•Environmental chitin spontaneously accumulates in airways lacking AMCase•Persistent immune activation and age-related fibrosis develop in the absence of AMCase•Mice with fibrotic lung disease and humans with ILD accumulate chitin in airways An ancient enzyme protects the lungs from damaging effects of a widespread environmental polysaccharide.