A novel anti-inflammatory role for secretory phospholipase A2 in immune complex-mediated arthritis.
Phospholipase A2 (PLA2) catalyses the release of arachidonic acid for generation of lipid mediators of inflammation and is crucial in diverse inflammatory processes. The functions of the secretory PLA2 enzymes (sPLA2), numbering nine members in humans, are poorly understood, though they have been shown to participate in lipid mediator generation and the associated inflammation. To further understand the roles of sPLA2 in disease, we quantified the expression of these enzymes in the synovial fluid in rheumatoid arthritis and used gene-deleted mice to examine their contribution in a mouse model of autoimmune erosive inflammatory arthritis. Contrary to expectation, we find that the group V sPLA2 isoform plays a novel anti-inflammatory role that opposes the pro-inflammatory activity of group IIA sPLA2. Mechanistically, group V sPLA2 counter-regulation includes promotion of immune complex clearance by regulating cysteinyl leukotriene synthesis. These observations identify a novel anti-inflammatory function for a PLA2 and identify group V sPLA2 as a potential biotherapeutic for treatment of immune-complex-mediated inflammation.
Boilard
Eric
E
Division of Rheumatology, Immunology and Allergy and Partners Asthma Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Lai
Ying
Y
Larabee
Katherine
K
Balestrieri
Barbara
B
Ghomashchi
Farideh
F
Fujioka
Daisuke
D
Gobezie
Reuben
R
Coblyn
Jonathan S
JS
Weinblatt
Michael E
ME
Massarotti
Elena M
EM
Thornhill
Thomas S
TS
Divangahi
Maziar
M
Remold
Heinz
H
Lambeau
Gérard
G
Gelb
Michael H
MH
Arm
Jonathan P
JP
Lee
David M
DM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054497:Phospholipases A2, Secretory / Q000235:genetics / Q000276:immunology*; D013582:Synovial Fluid / Q000201:enzymology / Q000276:immunology
D000893:Anti-Inflammatory Agents; D000936:Antigen-Antibody Complex; D054497:Phospholipases A2, Secretory