The function of the lung is dependent upon differentiation and proliferation of respiratory epithelial cells and the synthesis/secretion of surfactant lipids and proteins into air space. During the respiratory inflammatory response, cytokines produced by macrophages and epithelial cells in the respiratory system have significant influence on surfactant protein homeostasis. We report here that among family members of Janus family tyrosine kinase (JAK) and signal transducers and activators of transcription (STAT), only JAK 1 and STAT3 stimulated the ؊500 to ؉41 promoter activity of the surfactant protein B (SP-B) gene in respiratory epithelial cells. JAK1 and STAT3 were co-localized in alveolar type II epithelial cells where SP-B is synthesized and secreted. Interleukin 6 and interleukin 11, known to activate STAT3 synergistically, stimulated the SP-B promoter activity with retinoic acid, which is at least partially mediated through interactions between STAT3 and retinoid nuclear receptor enhanceosome proteins in pulmonary epithelial cells.The lung has the largest epithelial surface area of the body in order to facilitate air exchange. The structure of alveoli is protected by surfactant membrane. Pulmonary surfactant is a complex mixture of lipids and proteins that form an insoluble film to reduce surface tension at the air/liquid interface in the alveoli. The reduction of surface tension at the alveolar surface promotes lung expansion on inspiration and prevents lung collapse on expiration. Deficiency of pulmonary surfactant is responsible for increased surface tension along the alveolar epithelium and brings about alveolar collapse and epithelial cell lysis, resulting in respiratory distress syndrome, a major cause of morbidity and mortality in preterm infants. Pulmonary surfactant is composed of 90 -95% lipids and 5-10% proteins. Among surfactant proteins, SP-B 1 is a 79-amino acid amphipathic peptide produced by the proteolytic cleavage of proSP-B in alveolar type II and Clara epithelial cells. The SP-B peptide is stored in lamellar bodies and secreted with phospholipids into the airway lumen. It facilitates the stability and rapid spreading of surfactant phospholipids during respiratory cycles (1). SP-B plays a critical role in postnatal lung function.

This study investigates the importance of thioesterlinked acyl groups in lung surfactant protein C (SP-C) in facilitating interactions with phospholipids that yield functionally important surface active behaviors. Native SP-C, palmitoylated at cysteine residues at positions 5 and 6, was isolated from bovine lung surfactant by liquid chromatography.

Type II cells and macrophages are the major cells involved in the alveolar clearance and catabolism of surfactant. We measured type II cell and macrophage contributions to the catabolism of saturated phosphatidylcholine and surfactant protein A (SP-A) in mice. We used intratracheally administered SP-A labeled with residualizing (125)I-dilactitol-tyramine, radiolabeled dipalmitoylphosphatidylcholine ([(3)H]DPPC), and its degradation-resistant analog [(14)C]DPPC-ether. At 15 min and 7, 19, 29, and 48 h after intratracheal injection, the mice were killed; alveolar lavage was then performed to recover macrophages and surfactant. Type II cells and macrophages not recovered by the lavage were subsequently isolated by enzymatic digestion of the lung. Radioactivity was measured in total lung, lavage fluid macrophages, alveolar washes, type II cells, and lung digest macrophages. Approximately equal amounts of (125)I-dilactitol-tyramine-SP-A and [(14)C]DPPC-ether associated with the macrophages (lavage fluid plus lung digest) and type II cells when corrected for the efficiency of type II cell isolation. Eighty percent of the macrophage-associated radiolabel was recovered from lung digest macrophages. We conclude that macrophages and type II cells contribute equally to saturated phosphatidylcholine and SP-A catabolism in mice.

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The relative contributions of zwitterionic and anionic phospholipids to the surface-active function of calf lung surfactant extract (CLSE) were assessed by measurements of surface properties in vitro and pressure-volume (P-V) mechanics in excised rat lungs in situ. Surface activity and mechanical effects were compared for chromatographically purified CLSE subfractions containing the complete mix of phospholipids (PPL) or modified phospholipids depleted in anionic components (mPPL), alone or combined with 1.3% (by weight) of hydrophobic surfactant proteins (SP-B and SP-C). Surface pressure-time (pi-t) adsorption isotherms at 37 degrees C were very similar for dispersions of PPL and mPPL in a Teflon dish with a stirred subphase to minimize diffusion resistance. Combination of either PPL or mPPL with hydrophobic SP substantially improved adsorption, but mixtures of PPL:SP and mPPL:SP had only small differences in pi-t isotherms and reached the same final equilibrium pi of approximately 47 mN/m achieved by CLSE. Surface pressure-area (pi-A) isotherms and maximum surface pressures were also very similar for spread films of PPL versus mPPL and PPL:SP versus mPPL:SP on the Wilhelmy balance (23 degrees C and 37 degrees C). Respreading based on pi-A isotherm area calculations was slightly better in surface-excess films of PPL versus mPPL and PPL:SP versus mPPL:SP, but differences were minor and were smaller at 37 degrees C than at 23 degrees C. Overall dynamic surface activity in oscillating bubble studies was not significantly different for PPL versus mPPL or for PPL:SP versus mPPL:SP, and the latter two mixtures both reached minimum surface tensions< 1 mN/m (37 degrees C, 20 cycles/min, 0.5 mM phospholipid). Dispersions of PPL:SP, mPPL:SP, and CLSE were also not significantly different in improving P-V mechanics almost to normal when instilled in lavaged, excised rat lungs at 37 degrees C (30 mg/2.5 ml saline). These data suggest that zwitterionic phospholipids have a major role over anionic phospholipids in interacting with hydrophobic SP in the adsorption, dynamic surface tension lowering, film respreading, and pulmonary mechanical activity of the hydrophobic components of calf lung surfactant in CLSE.