Secretory phospholipase A2 induces dendritic cell maturation

High level of phospholipase A2 (PLA2) activity is found in serum and biological fluids during the acute-phase response (APR). Extracellular PLA2 in fluids of patients with inflammatory diseases such as sepsis, acute pancreatitis or rheumatoid arthritis is also associated with propagation of inflammation. PLA2 activity is involved in the release of both pro- and anti-inflammatory lipid mediators from phospholipids of cellular membranes or circulating lipoproteins. PLA2 may thus generate signals that influence immune responses. Here, group III secretory PLA2 were tested for their ability to promote generation of functionally mature human dendritic cells (DC). PLA2 treatment of differentiating monocytes in the presence of granulocyte/macrophage colony-stimulating factor and IL-4 yielded cells with phenotypical and functional characteristics of mature DC. This maturation was dependent on the dose of PLA2, and PLA2-generated DC stimulated IFN-γ secretion by allogeneic T cells. The effects of PLA2 on DC maturation was mainly dependent on enzyme activity and correlated with the activation of NF-κB, AP-1 and NFAT. The data suggest that transient increase in PLA2 activity generates signals that promote transition of innate to adaptive immunity during the APR. © 2004 Wiley-VCH Verlag GmbH & Co. KGaA.