[Surfactant-associated proteins B and C: molecular biology and physiologic properties].
Treatment of neonatal RDS in premature infants with intratracheal administration of natural surfactant has become gold standard therapy. Natural surfactant preparations mainly contain, apart from phospholipids, the surfactant associated proteins B and C (SP-B and SP-C). Both proteins are synthesized mainly in alveolar type-II cells and Clara-cells, SP-B, also in the gastrointestinal tract and the auditive tube. SP-B is encoded on chromosome 2 over a region with 11 exons, whereas the SP-C gene is localized on chromosome 8 in a region containing 6 exons. Transcription of both SP-B and SP-C is induced by TTF-1. Furthermore SP-1 and SP-3 are known as transcription factors for SP-B. The main function of SP-B and SP-C is to maintain physiologic surface properties enabeling adequate lung mechanics. A complete SP-B deficiency following homozygous mutations in the SP-B gene (e. g. 121-ins 2-mutation) therefore leads to severe respiratory failure postnatally, due to the lack of functional surfactant. On the other hand complete deficiency of SP-C causes chronic interstitial pneumonitis as well in infants as in adults depending on disease-modifiers yet unknown. Besides the surface tension lowering property, SP-B reveals immunological functions regarding its interaction with different proinflammatory cellular systems as well as other inflammatory mediators, e. g. following hyperoxia. For SP-C first studies have described modulation of inflammatory reactions in macrophages, suggesting similar immune-modulatory effects. Whereas basic effects on lung mechanisms of both lipophilic surfactant proteins seem to be well understood, their immunologic local pulmonary functions and effects on surfactant metabolism require further investigations.
Gortner
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L
Abteilung für Neonatologie und Pädiatrische Intensivmedizin, Zentrum für Kinderheilkunde und Jugendmedizin der Justus-Liebig-Universität Giessen, Giessen. kilgor@uniklinik-saarland.de
Hilgendorff
A
A
D000328:Adult; D000818:Animals; D002889:Chromosomes, Human, Pair 2; D002898:Chromosomes, Human, Pair 8; D004252:DNA Mutational Analysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017563:Lung Diseases, Interstitial / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D010455:Peptides / Q000235:genetics* / Q000502:physiology / Q000627:therapeutic use; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics* / Q000502:physiology / Q000627:therapeutic use; D037721:Pulmonary Surfactant-Associated Protein C; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D012131:Respiratory Insufficiency / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology
D010455:Peptides; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; C489679:SFTPC protein, human