Pulmonary surfactant is a complex mixture of lipids and proteins synthesized and secreted by alveolar type II cells. The major components of surfactant are phospholipids, and dipalmitoylphosphatidylcholine (DPPC) is believed to be especially essential for the surfactant function. There have been found four apoprotein components specific for pulmonary surfactant, i. e., surfactant protein A(SP-A), -B(SP-B), -C(SP-C) and -D(SP-D).
The purpose of this study was examine the relationship between SP-A or SP-D and phospholipid metabolism in alveolar type II cells. New findings obtained in the present study are summarized.
1. SP-A is a hydrophilic glycoprotein with a reduced denatured molecular mass of 26-38 kDa in the rat. This protein possesses the striking structure of collagen-like sequences in the aminoterminal region and C-type lectin sequences in the carboxy-terminal region. The present study showed that the collagenous region is especially important for the biological activities, i. e.,
receptor binding and suppression of phospholipid secretion, of SP-A. This result suggests that a macromolecular structure maintained by the collagenous structure is essential for the SP-A function.
2. SP-A possesses a possible lipid binding domain after the collagenous region. This study presented the direct evidence-that SP-A binds phosphatidylcholine and sphingomyelin, especially exhibits a strong binding to DPPC ; - suggesting that SP-A plays an important role in the regulation of recycling and intra- and extracellular movement of DPPC. Liposomes containing DPPC were preferentially taken up in the presence of SP-A by alveolar type II cells. The DPPC-containing liposomes also bound preferentially to plasma membranes of type II cells with SP-A.
3. SP-D is also a hydrophilic glycoprotein that shows structural similarities to SP-A in its collagenous domain and carbohydrate binding property. The present study showed that, in spite of structural similarities between SP-A and SP-D, the distribution of SP-D in the lavage fluid is clearly different from that of SP-A, that is, significant amounts of SP-D is soluble in the lavages and bind phospholipids in the soluble form. Native SP-D is present with lipids in soluble form.
4. Native SP-D affected neither basal secretion nor stimulated secretion by alveolar type 11 cells. However, native SP-D counteracted the inhibitory effect of SP-A on surfactant secretion. Excess native SP-D competed with iodine-labelled SP-A for receptor binding to type II cells. Butanol extraction of native SP-D decreased significantly the SP-D activity. The butanol-soluble fraction of native SP-D possessed the ability to alter the inhibitory effect of S97-A to the same extent as native SP-D. We conclude that native SP-D, bound lipids, alters SP-A activity in type II cells through interaction with it via SP-D-associated lipids. Less