Importance of group X-secreted phospholipase A2 in allergen-induced airway inflammation and remodeling in a mouse asthma model.
Arachidonic acid metabolites, the eicosanoids, are key mediators of allergen-induced airway inflammation and remodeling in asthma. The availability of free arachidonate in cells for subsequent eicosanoid biosynthesis is controlled by phospholipase A(2)s (PLA(2)s), most notably cytosolic PLA(2)-alpha. 10 secreted PLA(2)s (sPLA(2)s) have also been identified, but their function in eicosanoid generation is poorly understood. We investigated the role of group X sPLA(2) (sPLA(2)-X), the sPLA(2) with the highest in vitro cellular phospholipolysis activity, in acute and chronic mouse asthma models in vivo. The lungs of sPLA(2)-X(-/-) mice, compared with those of sPLA(2)-X(+/+) littermates, had significant reduction in ovalbumin-induced infiltration by CD4(+) and CD8(+) T cells and eosinophils, goblet cell metaplasia, smooth muscle cell layer thickening, subepithelial fibrosis, and levels of T helper type 2 cell cytokines and eicosanoids. These data direct attention to sPLA(2)-X as a novel therapeutic target for asthma.
Henderson
William R
WR
Center for Allergy and Inflammation, Department of Medicine, University of Washington, Seattle, WA 98109, USA. joangb@u.washington.edu
Chi
Emil Y
EY
Bollinger
James G
JG
Tien
Ying-tzang
YT
Ye
Xin
X
Castelli
Luca
L
Rubtsov
Yuri P
YP
Singer
Alan G
AG
Chiang
Gertrude K S
GK
Nevalainen
Timo
T
Rudensky
Alexander Y
AY
Gelb
Michael H
MH
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D054509:Group X Phospholipases A2; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D008679:Metaplasia / Q000201:enzymology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010741:Phospholipases A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D018418:Th2 Cells / Q000201:enzymology
D000485:Allergens; D016207:Cytokines; D015777:Eicosanoids; D010741:Phospholipases A; D054509:Group X Phospholipases A2; D054467:Phospholipases A2; C516366:Pla2g10 protein, mouse