Myeloid-specific deletion of group VIA calcium-independent phospholipase A2 induces pro-inflammatory LPS response predominantly in male mice via MIP-1

Polymorphisms of group VIA calcium-independent phospholipase A2 (PLA2G6) are associated with blood C-reactive protein suggesting its role in inflammation. We showed that myeloid-specific Pla2g6-deficiency in Pla2g6(M-/-) mice led to exaggerated inflammation and fibrosis in a lean fatty liver model. We here investigated whether these mutants display alteration in immune response after treatment with E. coli lipopolysaccharides (LPS) under acute (a single dose) and persistent (four doses) conditions. Without LPS treatment, male Pla2g6(M-/-) (but not Flox) mice at 12 months of age exhibited splenomegaly and hepatic necrosis, and ~ 30 % of them exhibited autoimmune hepatitis showing lymphoplasma cells with CD3(+) and CD45R(+) staining. Under acute LPS, male mutants showed an elevation of plasma MIP-1

• Klement, L.
• Jansakun, C.
• Yan, B.
• Staffer, S.
• Tuma-Kellner, S.
• Altamura, S.
• Muckenthaler, M.
• Merle, U.
• Chamulitrat, W.