N-Terminally Extended Surfactant Protein (SP) C Isolated from SP-B-Deficient Children Has Reduced Surface Activity and Inhibited Lipopolysaccharide Binding

Jing Li, Machiko Ikegami, Cheng Lun Na, Aaron Hamvas, Quentin Espinassous, Richard Chaby, Lawrence M. Nogee, Timothy E. Weaver, Jan Johansson

Research output: Contribution to journalArticle


In both humans and mice, a deficiency of surfactant protein B (SP-B) is associated with a decreased concentration of mature SP-C and accumulation of a larger SP-C peptide, denoted SP-Ci, which is not observed under normal conditions. Isolation of hydrophobic polypeptides from the lungs of children who died with two different SP-B mutations yielded pure SP-C i and showed only trace amounts of mature SP-C. Determination of the SP-Ci covalent structure revealed a 12-residue N-terminal peptide segment, followed by a 35-residue segment that is identical to mature SP-C. The SP-Ci structure determined herein is similar to that of a proposed late intermediate in the processing of proSP-C, suggesting that SP-C i is the immediate precursor of SP-C. In bronchoalveolar lavage fluid from transgenic mice with a focal deficiency of SP-B, SP-Ci was detected in the biophysically active, large aggregate fraction and was associated with membrane structures that are typical for a large aggregate surfactant. However, unlike SP-C, SP-Ci exhibited a very poor ability to promote phospholipid adsorption, gave high surface tension during cyclic film compression, and did not bind lipopolysaccharide in vitro. SP-C i is thus capable of associating with surfactant lipids, but its N-terminal dodecapeptide segment must be proteolytically removed to generate a biologically functional peptide. The results of this study indicate that the early postnatal fatal respiratory distress seen in SP-B-deficient children is combined with the near absence of active variants of SP-C.

Original languageEnglish (US)
Pages (from-to)3891-3898
Number of pages8
Issue number13
StatePublished - Apr 6 2004


ASJC Scopus subject areas

  • Biochemistry

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