Hydrolysis of surfactant-associated phosphatidylcholine by mammalian secretory phospholipases A2.
Hydrolysis of surfactant-associated phospholipids by secretory phospholipases A2 is an important potential mechanism for surfactant dysfunction in inflammatory lung diseases. In these conditions, airway secretory phospholipase A2 (sPLA2) activity is increased, but the type of sPLA2 and its impact on surfactant function are not well understood. We examined in vitro the effect of multiple secretory phospholipases A2 on surfactant, including their ability to 1) release free fatty acids, 2) release lysophospholipids, and 3) increase the minimum surface tension (gammamin) on a pulsating bubble surfactometer. Natural porcine surfactant and Survanta were exposed to mammalian group I (recombinant porcine pancreatic) and group II (recombinant human) secretory phospholipases A2. Our results demonstrate that mammalian group I sPLA2 hydrolyzes phosphatidylcholine (PC), producing free fatty acids and lysophosphatidylcholine, and increases gammamin. In contrast, mammalian group II sPLA2 demonstrates limited hydrolysis of PC and does not increase gammamin. Group I and group II secretory phospholipases A2 from snake venom hydrolyze PC and inhibit surfactant function. In summary, mammalian secretory phospholipases A2 from groups I and II differ significantly from each other and from snake venom in their ability to hydrolyze surfactant-associated PC.
Hite
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Section on Pulmonary and Critical Care, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Seeds
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Jacinto
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Balasubramanian
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Waite
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Bass
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D000818:Animals; D001688:Biological Products; D019556:COS Cells; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D054501:Group II Phospholipases A2; D006801:Humans; D006868:Hydrolysis; D008168:Lung / Q000201:enzymology; D008246:Lysophospholipids / Q000378:metabolism; D008322:Mammals; D010179:Pancreas / Q000201:enzymology; D010713:Phosphatidylcholines / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012910:Snake Venoms; D013379:Substrate Specificity; D013500:Surface Tension; D013552:Swine; D014162:Transfection
D001688:Biological Products; D005230:Fatty Acids, Nonesterified; D008246:Lysophospholipids; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D012910:Snake Venoms; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2; C072197:beractant