PULMONARY HYDROPHOBIC SURFACTANT-ASSOCIATED PROTEINS

摘要

Novel, isolated, substantially pure, hydrophobic surfactant-associated proteins of 4,000-7,000 dalton simple molecular weight, SAP(Val) and SAP(Phe); multimers thereof, and substitution, addition and deletion analogs and fragments thereof. When SAP(Val) and/or SAP(Phe) is combined with lipids, its surfactant-like property imparts to the combination significant pulmonary biophysical activity. Such a combination results in enhanced adsorption of the lipids with properties similar to that of natural pulmonary surfactant material. SAP(Val) and/or SAP(Phe) in combination with lipids is highly useful for replacing or supplementing natural pulmonary surfactant material for reducing or maintaining normal surface tension in the lungs, especially in the lungs of patients suffering from hyaline membrane disease, HMD, or other syndromes associated with the lack or insufficient amounts of natural pulmonary surfactant material. A combination of SAP(Val) and/or SAP(Phe) and lipids may be administered as an aerosol spray or in aqueous normal saline with or without calcium chloride for treating or preventing HMD and other surfactant deficiency states. Also disclosed are methods of isolating the SAP(Val) from animal tissue and methods for making SAP(Val) and SAP(Phe) by recombinant DNA techniques and direct peptide synthesis; genomic clones of SAP(Val) and SAP(Phe); expression systems and products for SAP(Val) DNA; and polyclonal and monoclonal antibodies to SAP(Val) and SAP(Phe).