Alteration of the Pulmonary Surfactant System in Full-Term Infants with Hereditary ABCA3 Deficiency

• DOI: 10.1164/rccm.200509-1535oc
• Publication Date: 2006-05-26T01:06:04Z
• Authors: Frank Brasch; Sven Schimanski; Christian Mühlfeld; Stefan Barlage; Thomas Langmann; Charalampos Aslan...; Alfred Boettcher; Ashraf Dada; Horst Schroten; Eva Mildenberger; Eric Prueter; Manfred Ballmann; Matthias Ochs; Georg Johnen; Matthias Griese; Gerd Schmitz
• Keywords: Surfactant protein C

ABCA3 mutations are known to cause fatal surfactant deficiency.We studied protein expression in full-term newborns with unexplained respiratory distress syndrome (URDS) as well the relevance of for homeostasis.Lung tissue infants URDS was analyzed type II pneumocytes. Coding exons gene were sequenced. Surfactant by immunohistochemistry, immunoelectron microscopy, and Western blotting.ABCA3 found be greatly reduced or absent 10 14 URDS. Direct sequencing revealed distinct clustering within vulnerable domains protein. A strong precursors B (pro-SP-B) but only low levels aggregates mature (SP-B) electron-dense bodies pneumocytes found. Within matrix bodies, we detected SP-C (pro-SP-C) cathepsin D. SP-A localized small intracellular vesicles, not bodies. pro-SP-B shown accumulate intraalveolar space, whereas SP-B absent, respectively.Our data provide evidence that associated a deficiency also an abnormal processing routing SP-C, leading severe alterations homeostasis syndrome. To identify hereditary deficiency, suggest combined diagnostic approach including immunohistochemical, ultrastructural, mutation analysis.