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 sh...

Full description

Saved in:
Bibliographic Details
Published in:EMBO molecular medicine 2010-05, Vol.2 (5), p.172-187
Main Authors: Boilard, Eric, Lai, Ying, Larabee, Katherine, Balestrieri, Barbara, Ghomashchi, Farideh, Fujioka, Daisuke, Gobezie, Reuben, Coblyn, Jonathan S., Weinblatt, Michael E., Massarotti, Elena M., Thornhill, Thomas S., Divangahi, Maziar, Remold, Heinz, Lambeau, Gérard, Gelb, Michael H., Arm, Jonathan P., Lee, David M.
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - immunology
Antigen-Antibody Complex - immunology
arthritis
Arthritis, Rheumatoid - enzymology
Arthritis, Rheumatoid - genetics
Arthritis, Rheumatoid - immunology
autoimmunity
Disease Models, Animal
Female
Human health and pathology
Humans
inflammation
Life Sciences
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Phospholipases A2, Secretory - genetics
Phospholipases A2, Secretory - immunology
secreted phospholipase A2
Synovial Fluid - enzymology
Synovial Fluid - immunology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1757-4676
1757-4684
DOI:10.1002/emmm.201000072