Abstract
We examined the role of a cytosolic phospholipase A2 (cPLA2) in antigen-induced eosinophil infiltration of airways and in airway hyperresponsiveness to methacholine. Inhibition of cPLA2, or blockade of the platelet-activating factor (PAF) receptor, blocked antigen-induced airway hyperresponsiveness and suppressed eosinophil infiltration. Neither cyclooxygenase nor 5-lipoxygenase inhibition had either effect. We show here that, in antigen-sensitized guinea pigs, cPLA2 inhibition prevents both eosinophilic infiltration and subsequent airway hyperresponsiveness after antigen challenge. We also show that this effect is mediated by first-step hydrolysis of membrane phospholipid into lysophospholipid rather than by prostanoid or leukotriene metabolites of arachidonate.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens / administration & dosage
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Azepines / pharmacology
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Benzoquinones / pharmacology
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Bronchoconstriction / drug effects
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Bronchoconstriction / immunology
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Butyrophenones / pharmacology
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Eicosapentaenoic Acid / analogs & derivatives*
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Eicosapentaenoic Acid / pharmacology
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Enzyme Inhibitors / pharmacology
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Eosinophils / drug effects
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Eosinophils / immunology
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Eosinophils / physiology*
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Guinea Pigs
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Indomethacin / pharmacology
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Male
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Methacholine Chloride / pharmacology
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Phospholipases A / antagonists & inhibitors*
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Phospholipases A2
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Piperidines / pharmacology
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Respiratory Hypersensitivity / immunology
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Respiratory Hypersensitivity / pathology
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Respiratory Hypersensitivity / physiopathology
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Respiratory Hypersensitivity / prevention & control*
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Triazoles / pharmacology
Substances
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Antigens
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Azepines
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Benzoquinones
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Butyrophenones
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EPACOCF3
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Enzyme Inhibitors
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Piperidines
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Triazoles
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Methacholine Chloride
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E 6123
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2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone
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Eicosapentaenoic Acid
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Phospholipases A
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Phospholipases A2
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ebastine
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Indomethacin