Abstract

Mammalian surfactant is an incompletely defined mixture of lipids and associated proteins of molecular mass 35,000 Da and approximately 6,000 Da. Surfactant preparations which are highly effective in treating respiratory distress syndrome in premature infants lack the 35-kDa proteins, but contain the 6-kDa proteins. We isolated and partially sequenced one of these low molecular weight proteins from the lung lavage material of an alveolar proteinosis patient. Oligonucleotides deduced from the sequence were used as probes to isolate a human cDNA clone. The clone codes for a 42-kDa protein which contains the sequence of the 6-kDa protein. Messenger RNA coding for the 42-kDa protein was identified in human lung RNA by in vitro translation and immunoprecipitation of the translation products with an antiserum against purified bovine surfactant 6-kDa proteins. Immunoprecipitation of the 42-kDa primary translation product is inhibited by the presence of the bovine 6-kDa protein. These observations suggest a precursor-product relationship of the 42-kDa protein to one of the 6-kDa proteins.

Highlights

  • Respiratory distress syndrome denotes the clinical condition of pulmonary dysfunction in prematureinfants

  • Clinical studies showed the PSP-Aaspresent in reduced amountsin amniotic fluid samples taken shortly before the birth of infants who developed respiratory distress syndrome [26,27,28]

  • The surfactant preparations used therapeutically to treat respiratory distress syndrome have been made by extracting natural surfactant with organic solvents

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Summary

We postulate that

AlTTrc~G42mATGmAM?.TrccrGG4zcTGG4zmAxGlrmm is the precursor of PSP-B, a proteolipid [42], and that the. These hydrophilic regions may mask the hydrophobic portions, facilitating intracellular transport of the protein to lamellar bodies. The gene coding forthe PSP-A protein containasbinding sequence for the glucocorticoid receptor [46]. [18] first suggested theexistence of multiple low molecular mass surfactant proteins. The amino acid sequence of PSP-B is differenth,owever, from that obtainedfor bovine PSP-B [22]. It is not clearwhich of these proteins are in the surfactant preparations usceldinically.

ISOlatiOn Of CDNA Clone encodinga high mOleNlar weight preNrllOe
Were immunopracipitated and
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