Surfactantproteine SP-B und SP-C: Molekularbiologie und Physiologie

 

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Zusammenfassung

Die Behandlung des Atemnotsyndroms Frühgeborener mit Surfactantpräparationen ist etablierter Standard in der neonatologischen Intensivtherapie. Natürliche Surfactantpräparationen enthalten neben einem Phospholipidgemisch im Wesentlichen die lipophilen assoziierten Proteine B und C (SP-B und SP-C). Beide Proteine werden überwiegend in Typ II-Zellen und Clara-Zellen, SP-B aber auch in Zellen des Gastrointestinaltrakts und der Tuba auditiva synthetisiert. SP-B wird auf Chromosom 2 über 11 Exons kodiert, SP-C auf Chromosom 8 über 6 Exons. Wesentliche transkriptionsfördernde Faktoren sind für beide Gene TTF-1 (thyroid-transcription factor 1), darüber hinaus für SP-B die Transkriptionsfaktoren SP-1 und SP-3. Eine vitale Funktion der Surfactantproteine B und C besteht in der Aufrechterhaltung der alveolären Oberflächeneigenschaften im Rahmen der physiologischen Lungenmechanik. Ein kompletter SP-B-Mangel durch homozygote Mutationen im SP-B-Gen (z. B. 121-ins 2-Mutation) führt zu einem schweren postnatalen respiratorischen Versagen, bedingt durch den Mangel an oberflächenwirksamem funktionellem Surfactant. Ein kompletter Mangel an SP-C führt im Säuglings- bis Erwachsenenalter in Abhängigkeit von bisher unklaren Krankheitsmodifikatoren zu einer chronischen interstitiellen Pneumonitis.

Neben den oberflächenspannungsreduzierenden Eigenschaften kommt dem SP-B eine immunologische Funktion im Sinne einer Interaktion mit verschiedenen proinflammatorischen zellulären Systemen sowie weiteren Inflammationsmediatoren zu, z. B. nach Hyperoxie. Ebenso ergeben sich erste Hinweise auf eine modulierende Wirkung inflammatorischer Reaktionen von Makrophagen durch SP-C. Die Oberflächenaktivität der lipophilen Surfactantproteine scheint in den Grundzügen geklärt zu sein, während ihre lokale immunologische und metabolische Aktivität weiterer Untersuchungen bedarf.

Abstract

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.

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Prof. Dr. L. Gortner

Geschäftsführender Direktor

Universitätsklinik für Kinder- und Jugendmedizin

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Email: kilgor@uniklinik-saarland.de