The pulmonary surfactant proteins 000 D) and SP-C (4,000 D) accelerate surface film formation by surfactant phospholipids. We used cDNA probes to examine regulation of these proteins in human fetal lung. The mRNAs were detectable at 13 wk gestation and increased to -50% (SP-B) and -15% (SP-C) of adult levels at 24 wk. The mRNAs were detected only in lung of 11 dog tissues examined. When human fetal lung was cultured as explants without hormones, SP-B mRNA increased and SP-C mRNA decreased. Exposure for 48 h to glucocorticoids, but not other steroids, increased both SP-B mRNA (-4-fold) and SP-C mRNA (-30-fold) vs.controls. Half-maximal stimulation occurred with 1 nM dexamethasone and 300 nM cortisol for SP-B mRNA and at threeto fivefold higher concentrations for SP-C mRNA. Both stimulation and its reversal on removal of hormone were more rapid for SP-B than for SP-C. Terbutaline and forskolin increased SP-B mRNA but not SP-C mRNA. Levels of both mRNAs were much higher in type II cells than fibroblasts prepared from explants. Thus, the genes for SP-B and SP-C are expressed in vivo before synthesis of both SP-A (28,000-36,000 D) and surfactant lipids. Glucocorticoid induction of SP-B and SP-C mRNAs in type II cells appears to be receptor mediated but may involve different mechanisms.

Pulmonary surfactant is a lipid-protein complex that promotes alveolar stability by lowering the surface tension at the air-fluid interface in the peripheral air spaces. A group of hydrophobic surfactant-associated proteins has been shown to be essential for rapid surface film formation by surfactant phospholipids. We have purified a hydrophobic surfactant protein of :5 kDa that we term SP5 from bronchopulmonary lavage fluid from a patient with alveolar proteinosis and shown that it promotes rapid surface film formation by simple mixtures of phospholipids. We have derived the full amino acid sequence of human SP5 from the nucleotide sequence of cDNAs identified with oligonucleotide probes based on the NH2-terminal sequence of SP5. SP5 isolated from surfactant is a fragment of a much larger precursor protein (21 kDa). The precursor contains an extremely hydrophobic region of 34 amino acids that comprises most of the mature SP5. This hydrophobicity explains the unusual solubility characteristics of SP5 and the fact that it is lipid-associated when isolated from lung.Pulmonary surfactant is a phospholipid-protein complex that lowers surface tension at the air-liquid interface in the alveolus (1). The lipid composition of surfactant has been studied in detail (2), and the major lipid components by weight are dipalmitoylphosphatidylcholine, monoenoic phosphatidylcholine, and phosphatidylglycerol. Four surfactant protein species have been identified in canine and human bronchoalveolar lavage. The most abundant species is a glycoprotein with a collagen-like 4). This protein has been shown to enhance uptake of surfactant lipids into alveolar type II cells (5) and inhibit secretion of surface-active material from these cells (6). The three other surfactant proteins, SP5 (5 kDa), SP8 (8 kDa), and SP18 (18 kDa), are very hydrophobic and have proved difficult to purify to homogeneity. The NH2-terminal amino acid sequences of the canine hydrophobic proteins have been determined, and it was shown that SP5 and SP8 share a common NH2 terminus (7). The complete amino acid sequence of SP18 deduced from canine and human cDNA sequences does not contain any region corresponding to the NH2 terminus of SP5 or SP8 (7,8).Various groups have studied the ability of the surfactant proteins to enhance surface activity of phospholipids in vitro using a surface balance. It has been shown that the small molecular weight hydrophobic proteins isolated from bovine surfactant enhance surface film formation by phospholipids (9-12). We have shown that mixtures of SP5, -8, and -18 or that SP18 alone, isolated from canine surfactant, stimulated phospholipid surface film formation (7). Unfortunately, detailed comparison of data between groups is difficult due to different methods of isolation and characterization of surfactant proteins.In this article we report the effect of purified human SP5 on the surface activity of simple phospholipid mixtures and the amino acid sequence of the precursor of SP5 derived from the sequences of near full-leng...