Inhibitory effects of surfactant protein A on surfactant phospholipid hydrolysis by secreted phospholipases A2.
Hydrolysis of surfactant phospholipids by secreted phospholipases A(2) (sPLA(2)) contributes to surfactant dysfunction in acute respiratory distress syndrome. The present study demonstrates that sPLA(2)-IIA, sPLA(2)-V, and sPLA(2)-X efficiently hydrolyze surfactant phospholipids in vitro. In contrast, sPLA(2)-IIC, -IID, -IIE, and -IIF have no effect. Since purified surfactant protein A (SP-A) has been shown to inhibit sPLA(2)-IIA activity, we investigated the in vitro effect of SP-A on the other active sPLA(2) and the consequences of sPLA(2)-IIA inhibition by SP-A on surfactant phospholipid hydrolysis. SP-A inhibits sPLA(2)-X activity, but fails to interfere with that of sPLA(2)-V. Moreover, in vitro inhibition of sPLA(2)-IIA-induces surfactant phospholipid hydrolysis correlates with the concentration of SP-A in surfactant. Intratracheal administration of sPLA(2)-IIA to mice causes hydrolysis of surfactant phosphatidylglycerol. Interestingly, such hydrolysis is significantly higher for SP-A gene-targeted mice, showing the in vivo inhibitory effect of SP-A on sPLA(2)-IIA activity. Administration of sPLA(2)-IIA also induces respiratory distress, which is more pronounced in SP-A gene-targeted mice than in wild-type mice. We conclude that SP-A inhibits sPLA(2) activity, which may play a protective role by maintaining surfactant integrity during lung injury.
Chabot
Sophie
S
Unité de Défense Innée et Inflammation, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale E 336, Paris, France.
Koumanov
Kamen
K
Lambeau
Gérard
G
Gelb
Michael H
MH
Balloy
Viviane
V
Chignard
Michel
M
Whitsett
Jeffrey A
JA
Touqui
Lhousseine
L
D000403:Airway Resistance / Q000235:genetics / Q000502:physiology; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D054501:Group II Phospholipases A2; D006868:Hydrolysis; D015151:Immunoblotting; D007442:Intubation, Intratracheal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010713:Phosphatidylcholines / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000037:antagonists & inhibitors / Q000378:metabolism; D010741:Phospholipases A / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D010743:Phospholipids / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000502:physiology; D037662:Pulmonary Surfactant-Associated Protein A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012128:Respiratory Distress Syndrome / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control
D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D010743:Phospholipids; D037662:Pulmonary Surfactant-Associated Protein A; D010741:Phospholipases A; D054501:Group II Phospholipases A2