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Published ahead of print on September 11, 2003, doi:10.1165/rcmb.2003-0262OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 30, pp. 449-458, 2004
© 2004 American Thoracic Society
DOI: 10.1165/rcmb.2003-0262OC

Surfactant Protein B in Type II Pneumocytes and Intra-Alveolar Surfactant Forms of Human Lungs

Frank Brasch, Georg Johnen, Alexandra Winn-Brasch, Susan H. Guttentag, Andreas Schmiedl, Nadine Kapp, Yasuhiro Suzuki, Klaus M. Müller, Joachim Richter, Samuel Hawgood and Matthias Ochs

Division of Electron Microscopy, Department of Anatomy, University of Göttingen, Göttingen; Institute of Pathology, University Hospital "Bergmannsheil," Bochum; Biochemical Pharmacology, Faculty of Science, Department of Biology, University of Konstanz, Konstanz, Germany; Department of Pediatrics and Cardiovascular Research Institute, University of California San Francisco, San Francisco, California; Division of Neonatology, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; and Department of Ultrastructural Research, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan

Address correspondence to: Frank Brasch, M.D., Institute of Pathology, University Hospital "Bergmannsheil", Bürkle-de-la-Camp Platz 1, D-44789 Bochum, Germany. 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) that is proteolytically processed to an 8-kD 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 endoplasmic reticulum, 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.

Abbreviations: bronchoalveolar lavage, BAL • composite bodies, cb • recombinant C-terminal propeptide of proSP-B, CproSP-B • immunoelectron microscopy, immuno-EM • lamellar bodies, lb • multivesicular bodies, mvb • recombinant N-terminal propeptide of proSP-B, NproSP-B • surfactant protein B, SP-B




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