The Action of Lung Lysosomal Phospholipases on Dipalmitoyl Phosphatidylcholine and its Significance for the Synthesis of Pulmonary Surfactant

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Abstract
Summary: Subcellular fractions were prepared from rabbit lung and characterized by marker enzyme assays. Phospholipases A of lysosomal type (active at pH 4.0 in the absence of Ca2+) show a peak of specific activity in fraction P3 (13000 X g; 20 min; pellet). About 70% of the phospholipase A activity of P3 can be obtained in a soluble extract. The rates of hydrolysis of dipalmitoyl (saturated) and unsaturated phosphatidylcholine molecules, presented to enzyme preparations in liposomes of varying composition, are shown in Tables 3 to 5. Although the rate for unsaturated molecules is unaffected by liposome composition, saturated molecules are hydrolyzed significantly faster in 5 mol % dipalmitoyl phosphatidylcholine liposomes than in 95 mol %. With enzyme preparation I (60% A1; 40% A2) the increase was 6-fold (P < 0.01). Preparations I and II hydrolyzed both kinds of molecules at similar rates in 50 mol % dipalmitoyl phosphatidylcholine liposomes, but preparation III, with a higher proportion of A2 (80%), gave a notably lower rate of hydrolysis of saturated molecules. Phosphatidylglycerol (10 mol %) also decreased the rate of hydrolysis of saturated molecules. These results are discussed in relation to fluidity of the liposomes and to the functions of the lysosomal-type phospholipases A of the lamellar inclusion bodies of the lung. Speculation: In lamellar bodies, phospholipase A2 will preferentially hydrolyze unsaturated phosphatidylcholine, yielding a lysolipid which can be reacylated to produce dipalmitoyl phosphatidylcholine; phospholipase A1 will require further inhibition, possibly provided by the phosphatidylglycerol of surfactant. Failure of A2 action or failure of the inhibition of A1 would be expected to lead to a deficiency of surfactant and thus to the respiratory distress syndrome in the newborn.