Platelet Activating Factor (PAF), a lipid with the structure of a 1-0-alkyl-2-acetyl phosphocholine (AGEPC), is capable of exerting potent effects on cardiopulmonary function in concentrations as low as 10-10M. In previous studies we found that PAF activity is present in pulmonary surfactant isolated from adult dog and rabbit lavage fluid. We propose three groups of experiments, each based on the results of Preliminary experiments. First, we have found that PAF is rapidly metabolized by Type II cells to a particular long-chain acyl glycerylether phosphocholine. Our proposed experiments will explore the enzyme pathways associated with this process. Second, observations recently obtained in our laboratory indicate that Type II cells also synthesize PAF. We will continue with these studies, determine whether substances which stimulate calcium movements may affect the pathways or kinetics of synthesis, and describe details of enzymatic sequences. Our third group of experiments will explore the effects of PAF on the metabolism of pulmonary surfactant. We have found that 10-9M PAF induces a 5-fold increase in surfactant secretion by Type II cells in primary culture. We will continue to define this process. PAF has been shown in some cell types to increase the activity of protein kinase C and to accelerate the turnover of phosphatidylinositol (PI) and its phosphorylated products. The activation of protein kinase C has also been shown to be associated with a stimulation of the secretion of pulmonary surfactant. For this reason we will determine whether the effects of PAF on the synthesis and secretion of pulmonary surfactant are associated with changes in PI metabolism or the activation of protein kinase C.
| Qualy, J M; Westfall, T C (1995) Overflow of endogenous norepinephrine from PVH nucleus of DOCA-salt hypertensive rats. Am J Physiol 268:H1549-54 |
| Everett, M M; King, R J; Jones, M B et al. (1990) Lung fibroblasts from animals breathing 100% oxygen produce growth factors for alveolar type II cells. Am J Physiol 259:L247-54 |
| King, R J; Jones, M B; Minoo, P (1989) Regulation of lung cell proliferation by polypeptide growth factors. Am J Physiol 257:L23-38 |
