Lysophosphatidylcholine sensitizes lipid extracts of pulmonary surfactant to inhibition by serum proteins.
Interactions between serum protein and lysophospholipid inhibitors of pulmonary surfactant were examined in vitro using a pulsating bubble surfactometer. In previous studies a particular batch of Lipid Extract Surfactant (LES) was observed to be unusually sensitive to inhibition by fibrinogen. This sample was found to contain an abnormally high concentration of lysophosphatidylcholine (lysoPC). Addition of exogenous lysophospholipid to LES at similar concentrations sensitized the surfactant to inhibition by fibrinogen. Sensitization to inhibition by lysoPC is also observed with fetal bovine serum. Under the conditions used, inhibition by bovine serum albumin was not affected. Whereas only small amounts of lysoPC (1 mol% added) maximally sensitize LES to inhibition by fibrinogen, co-addition of equal amounts of palmitic acid can partially offset this effect at low lysoPC concentrations (less than 5 mol%). Lipid Extract Surfactant was digested with phospholipase A2 to mimic the generation of endogenous lysoPC at the expense of surfactant lipids. Digestion of 2-3% of the phosphatidylcholine to lysophosphatidylcholine vastly sensitized the surfactant to inhibition by fibrinogen. These results suggest that the degradation of surfactant phospholipids by phospholipase A2 to lysophospholipids could contribute to the development and progression of adult and neonatal respiratory distress syndromes.
Cockshutt
A M
AM
Department of Biochemistry, University of Western Ontario, London, Canada.
Possmayer
F
F
D000818:Animals; D001798:Blood Proteins / Q000502:physiology*; D002417:Cattle; D005340:Fibrinogen / Q000302:isolation & purification / Q000502:physiology; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000378:metabolism; D013500:Surface Tension
D001798:Blood Proteins; D008244:Lysophosphatidylcholines; D011663:Pulmonary Surfactants; D005340:Fibrinogen; D010741:Phospholipases A; D054467:Phospholipases A2