VERY-LOW-DENSITY LIPOPROTEINS STIMULATE SURFACTANT LIPID-SYNTHESIS IN-VITRO

Surfactant synthesis is critically dependent on the availability of fa tty acids. One fatty acid source may be circulating triglycerides that are transported in VLDL, and hydrolyzed to free fatty acids by lipopr otein lipase (LPL). To evaluate this hypothesis, we incubated immortal ized or primary rat alveolar pre-type II epithelial cells with VLDL. T he cells were observed to surface bind, internalize, and degrade VLDL, a process that was induced by exogenous LPL. LPL induction of lipopro tein uptake significantly increased the rates of choline incorporation into phosphatidylcholine (PC) and disaturated PC, and these effects w ere associated with a threefold increase in the activity of the rate-r egulatory enzyme for PC synthesis, cytidylyltransferase. Compared with native LPL, a fusion protein of glutathione S-transferase with the ca talytically inactive carboxy-terminal domain of LPL did not activate C T despite inducing VLDL uptake. A variant of the fusion protein of glu tathione S-transferase with the catalytically inactive carboxy-termina l domain of LPL that partially blocked LPL-induced catabolism of VLDL via LDL receptors also partially blocked the induction of surfactant s ynthesis by VLDL. Taken together, these observations suggest that both the lipolytic actions of LPL and LPL-induced VLDL catabolism via lipo protein receptors might play an integral role in providing the fatty a cid substrates used in surfactant phospholipid synthesis.