A Morphometric Study of Mucins and Small Airway Plugging in Cystic Fibrosis

Pierre-Régis Burgel ^1*, David Montani ¹, Claire Danel ², Daniel Dusser ¹ and Jay A Nadel ³

¹ Hôpital Cochin, Université René Descartes, France
² Hôpital Européen Georges Pompidou, AP-HP, Paris, France
³ ardiovascular Research Institute and Departments of Medicine and Physiology, University of Californi, United States

^* To whom correspondence should be addressed. E-mail: burgelp{at}hotmail.com.

Accepted 16 August 2006

Abstract

Rationale: Little knowledge exists on structural changes and plugging in small airways in cystic fibrosis (CF).

Objective: To characterize the extent of plugging and contribution of secreted mucins to the plugs.

Methods: Small airways in CF subjects at transplantation (n=18) were compared to control non-smokers (n=10). Tissue sections were stained with Alcian blue (AB)/PAS, for mucins MUC5B and MUC5AC, and for neutrophils and its chemoattractant IL-8. EGFR and its ligand pro-TGF-alpha were also identified using immunohistochemistry. Epithelial and luminal contents were assessed morphometrically.

Results: Plugs occupying more than 50% of total luminal volume were found in 147 of 231 (63.6%) airways in CF subjects, but only in 1 of 39 (2.6%) airways in controls. In CF epithelium, AB/PAS-, MUC5B-, and MUC5AC-stained volume densities were increased ten-fold (P<0.01), indicating increased mucin production. In airway lumens, staining for mucins was also increased in CF, indicating increased mucin secretion. In CF epithelium, neutrophil numbers were markedly increased and were inversely correlated with volume densities of mucous glycoconjugates (r=-0.66, P<0.005). IL-8 staining was increased in CF epithelium and colocalized with mucins. Stained for EGFR and for pro-TGF-alpha were increased in CF epithelium; positive correlations were found between EGFR- and both AB/PAS- and IL-8-stained volume densities.

Conclusions: The majority of small airways are plugged in CF at the time of transplantation. Mucins contribute to airway plugging. Recruited neutrophils may be involved in mucin secretion in the plugs. Increased expression of EGFR and its ligand suggests roles in mucin synthesis and neutrophil recruitment.

Keywords: MUC5AC, MUC5B, airway epithelium, epidermal growth factor receptor, neutrophil

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