Secretory phospholipase A₂ induces dendritic cell maturation

Abstract

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 bothpro‐ and anti‐inflammatory lipid mediators from phospholipids of cellular membranes or circulating lipoproteins. PLA2 may thus generate signals that influence immune responses. Here, groupIII 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.

Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins

“…Mast cell-derived exosomes trigger functional maturation of dendritic cells ( 6 ). This maturation process involves secreted PLA 2 ( 13 ) and prostaglandins ( 14 ). Therefore, we investigated the presence of lipid-related proteins and lipid mediators on exosomes derived from the mast cell line RBL-2H3.…”

“…The DC maturation process has been shown to involve lysophosphatidylcholine and secreted PLA 2 ( 13 ), and prostaglandins ( 14 ). We previously reported that exosomes from RBL-2H3 cells contain a high amount of lysophosphatidylcholine (LPC) ( 15 ) and that phospholipase D was involved in exosome release ( 16 ).…”

Lysophosphatidylcholine is a natural adjuvant that initiates cellular immune responses

“…During the APR, increased oxidation of LDL and secretion of PLA 2 both favour the production of LPC and other biologically active lipids that have the ability to stimulate DC maturation [8,46]. Elevated levels of active LPC in the blood can result from oxidation or PLA 2 hydrolysis of PC from lipoproteins accompanied by a decrease in the concentration of LPC inhibitors, albumin and native LDL.…”

Multiple Roles of Phospholipase A2during Lung Infection and Inflammation

“…Certain PLA 2 groups also impact the adaptive immune system through the ability to activate signaling pathways that result in the generation of cytokines (94,97). The maturation of dendritic cells (DCs) from monocytes has been demonstrated to occur as a result of treatment with group III sPLA 2 s (94, 97).…”