Inhibition of pulmonary surfactant function by phospholipases.
Previous studies have shown that respiratory failure associated with disorders such as acute pancreatitis correlates well with increased levels of phospholipase A2 (PLA2) in lung lavages and that intratracheal administration of PLA2 generates an acute lung injury. In addition, bacteria such as Pseudomonas have been shown to secrete phospholipase C (PLC). We studied the effects of these phospholipases on pulmonary surfactant activity using a pulsating bubble surfactometer. Concentrations greater than or equal to 0.1 unit/ml PLA2 destroyed surfactant biophysical activity, increasing surface tension at minimum bubble size from less than 1 to 15 mN/m. This surfactant inactivation was predominantly related to the effect of lysophosphatidylcholine on the surface film, although the fatty acids released with higher PLA2 concentrations also had a detrimental effect on surfactant function. Similarly, as little as 0.1 unit PLC increased the surface tension at minimal size of an oscillating bubble from less than 1 to 15 mN/m, an effect that could be mimicked by the addition of dipalmitin to surfactant in the absence of PLC. Moreover, lower, noninhibitory concentrations (0.01 unit/ml) of PLA2 and PLC increased the sensitivity of surfactant to other inhibitory agents, such as albumin. Thus, relatively low concentrations of PLC and PLA2 can cause severe breakdown of surfactant function and may contribute significantly to some forms of lung injury.
Department of Gynecology/Obstetrics, State University of New York, Buffalo 14222.
B A
BA
Holm
L
L
Keicher
M Y
MY
Liu
J
J
Sokolowski
G
G
Enhorning
D000818:Animals; D002417:Cattle; D002855:Chromatography, Thin Layer; D006868:Hydrolysis; D066298:In Vitro Techniques; D010713:Phosphatidylcholines / Q000494:pharmacology; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000037:antagonists & inhibitors*; D013500:Surface Tension; D010738:Type C Phospholipases / Q000494:pharmacology
D010713:Phosphatidylcholines; D010743:Phospholipids; D011663:Pulmonary Surfactants; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases