Published ahead of print on September 11, 2003, doi:10.1165/rcmb.2003-0262OC Am. J. Respir. Cell Mol. Biol., Volume 30, Number 4, April 2004, 449-458 A more recent version of this article appeared on April 1, 2004
Submitted on July 11, 2003 Surfactant protein B in type II pneumocytes and intraalveolar surfactant forms of human lungsFrank Brasch1*,1 Division of Electron Microscopy, Department of Anatomy, University of Gottingen, Gottingen, Germany; Institute of Pathology, University Hospital, Bochum, Germany, 2 Institute of Pathology, University Hospital, Bochum, Germany, 3 Division of Neonatology, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, 4 Division of Electron Microscopy, Department of Anatomy, University of Gottingen, Gottingen, Germany, 5 Biochemical Pharmocology, Faculty of Science, Department of Biology, University of Konstanz, Konstanz, Germany, 6 Department of Ultrastructural Research, Inst. Frontier Medical Sciences, Kyoto University, Kyoto, Japan, 7 Department of Pediatrics and Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA * To whom correspondence should be addressed. E-mail: frank.e.brasch{at}ruhr-uni-bochum.de.
Surfactant protein B (SP-B) is synthesized by type II pneumocytes as a proprotein (proSP-B) which is proteolytically processed to a 8-kDa protein. In human type II pneumocytes, we identified not only proSP-B, processing intermediates of proSP-B, and mature SP-B but also fragments of the N-terminal propeptide. By means of immunoelectron microscopy, proSP-B and processing intermediates were localized in the ER, Golgi vesicles and few multivesicular bodies in type II pneumocytes in human lungs. A colocalization of fragments of the N-terminal propeptide and mature SP-B was found in multivesicular, composite and some lamellar bodies. Mature SP-B was localized over the projection core of lamellar bodies and core-like structures in tubular myelin figures. In line with immunoelectron microscopy and Western blot analysis of human type II pneumocytes, a fragment of the N-terminal propeptide was also detected in isolated rat lamellar bodies. In conclusion, our data indicate that the processing of proSP-B occurs between the Golgi complex and multivesicular bodies and provide evidence that a fragment of the N-terminal propeptide and mature SP-B are transported together to the lamellar bodies. In human lungs, mature SP-B is involved in the structural organization of lamellar bodies and tubular myelin by the formation of core particles.
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