Cathepsin H and napsin A are active in the alveoli and increased in alveolar proteinosis

¹ Childrens' Hospital of the Ludwig-Maximilians-University, Lindwurmstr. 4, 80337 Munich, Germany
² Hôpital Necker Enfants Malades, Service de Pneumologie et d'Allergologie Pédiatriques, 149 rue de Sèvres, 75015 Paris, France
³ ASKLEPIOS Fachkliniken, Zentrum für Pneumologie und Thoraxchirurgie, Robert-Koch-Allee 2, 82131 Munich, Germany

^* To whom correspondence should be addressed. E-mail: Matthias.griese{at}med.uni-muenchen.de.

	Abstract

Pulmonary alveolar proteinosis (PAP) is a group of rare diseases with a disturbed homeostasis of alveolar surfactant. While 90% of the primary adult forms are caused by GM-CSF auto-antibodies, the underlying cause of the juvenile form remains unknown. In order to distinguish primary from secondary effects in the pathogenesis of these two forms, we studied the surfactant protein processing proteases napsin A and cathepsin H.

We enrolled sixteen controls, 20 patients with the juvenile form of PAP, and 13 adults with idiopathic PAP. Amounts and activities of the proteases in the bronchoalveolar lavage fluid were determined by immunoblotting and specific substrate cleavage.

Both proteases were present and active in lavage fluid from controls and increased in PAP patients of both forms. The amount of active cathepsin H in relation to total cathepsin H was increased in PAP patients compared to controls. Cystatin C, the physiological inhibitor of cathepsin H in the alveolar space, was not increased to the same degree as cathepsin H, resulting in an imbalance of inhibitor to protease in the alveolar space.

A general defect in napsin A and cathepsin H expression or activity as the specific cause for abnormal surfactant accumulation in juvenile PAP was excluded.