Blockade of eosinophil migration and airway hyperresponsiveness by cPLA2-inhibition.
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.
Myou
S
S
Third Department of Internal Medicine, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan.
Sano
H
H
Fujimura
M
M
Zhu
X
X
Kurashima
K
K
Kita
T
T
Nakao
S
S
Nonomura
A
A
Shioya
T
T
Kim
K P
KP
Munoz
N M
NM
Cho
W
W
Leff
A R
AR
D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001381:Azepines / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology; D002090:Butyrophenones / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010880:Piperidines / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D014230:Triazoles / Q000494:pharmacology
D000941:Antigens; D001381:Azepines; D016227:Benzoquinones; D002090:Butyrophenones; C114733:EPACOCF3; D004791:Enzyme Inhibitors; D010880:Piperidines; D014230:Triazoles; D016210:Methacholine Chloride; C068033:E 6123; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D015118:Eicosapentaenoic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; C058249:ebastine; D007213:Indomethacin