AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 4 647-L656, Copyright © 1995 by American Physiological Society
Aberrant processing of surfactant protein C in hereditary SP-B deficiency
D. K. Vorbroker, S. A. Profitt, L. M. Nogee and J. A. Whitsett
Children's Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, Ohio 45229, USA.
Hereditary surfactant protein B (SP-B) deficiency causes lethal neonatal
respiratory disease associated with abnormalities in pulmonary surfactant
proteins and lipids. SP-C, a 4-kDa hydrophobic protein produced from a
21-kDa precursor, cooperates with SP-B to enhance the surface active
properties of surfactant phospholipids. Anti-proSP-C polyclonal antisera
were produced against fusion proteins containing 1) the amino terminus
(amino acids 1-20), 2) the region carboxy-terminal to the mature SP-C
peptide (amino acids 58-77), and 3) full-length 197-amino acid proSP-C and
were characterized using immunoprecipitation, Western blot, and
immunohistochemical techniques. Western blot analysis of bronchoalveolar
lavage and amniotic fluid from hereditary SP-B-deficient patients allowed
identification of a 12-kDa form of SP-C that contained epitopes consistent
with the amino-terminal and active peptide regions of SP-C (amino acids
1-57). The 12-kDa SP-C peptide was not detected in bronchoalveolar lavage
from healthy adults or adults with alveolar proteinosis or pneumonia. We
conclude that SP-B deficiency is associated with the aberrant processing
and secretion of an immature SP-C peptide, which may contribute to the
respiratory failure associated with hereditary SP-B deficiency.
