Blockade of eosinophil migration and airway hyperresponsiveness by cPLA2-inhibition.

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.

• Authors: S Myou, H Sano, M Fujimura, X Zhu, K Kurashima, T Kita, S Nakao, A Nonomura, T Shioya, K P Kim, N M Munoz, W Cho, A R Leff
• Journal: Nature immunology (Nat Immunol) Vol. 2 Issue 2 Pg. 145-9 (Feb 2001) ISSN: 1529-2908 [Print] United States
• PMID: 11175812 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens
• Azepines
• Benzoquinones
• Butyrophenones
• EPACOCF3
• Enzyme Inhibitors
• Piperidines
• Triazoles
• Methacholine Chloride
• E 6123
• 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone
• Eicosapentaenoic Acid
• Phospholipases A
• Phospholipases A2
• ebastine
• Indomethacin

Topics

• Animals
• Antigens (administration & dosage)
• Azepines (pharmacology)
• Benzoquinones (pharmacology)
• Bronchoconstriction (drug effects, immunology)
• Butyrophenones (pharmacology)
• Eicosapentaenoic Acid (analogs & derivatives, pharmacology)
• Enzyme Inhibitors (pharmacology)
• Eosinophils (drug effects, immunology, physiology)
• Guinea Pigs
• Indomethacin (pharmacology)
• Male
• Methacholine Chloride (pharmacology)
• Phospholipases A (antagonists & inhibitors)
• Phospholipases A2
• Piperidines (pharmacology)
• Respiratory Hypersensitivity (immunology, pathology, physiopathology, prevention & control)
• Triazoles (pharmacology)