Proinflammatory Macrophage-activating Properties of the Novel Phospholipid Diacylglycerol Pyrophosphate

Marı́A A Balboa,Jesús Balsinde,Deirdre A Dillon,George M Carman,Edward A Dennis

doi:10.1074/jbc.274.1.522

Abstract

We have found that the novel phospholipid diacylglycerol pyrophosphate (DGPP), identified in bacteria, yeast, and plants, but not in mammalian cells, is able to potently activate macrophages for enhanced secretion of arachidonate metabolites, a key event in the immunoinflammatory response of leukocytes. Macrophage responses to DGPP are specific and are not mediated by its conversion into other putative lipid mediators such as phosphatidic acid, lysophosphatidic acid, or diacylglycerol. The responses to DGPP are compatible with a receptor-recognition event because they are blocked by suramin. Intracellular signaling initiated by DGPP includes phosphorylation and activation of the Group IV cytosolic phospholipase A2 and of the extracellular-signal regulated p42 mitogen-activated protein kinase (MAPK) and p44 MAPK, and membrane translocation of the protein kinase C isoenzymes alpha, epsilon, delta. These results establish DGPP as a novel macrophage-activating factor and suggest a potential role for this compound in triggering homeostatic cellular responses.

Highlights

Leukocytes constitute the primary line of defense against infection
diacylglycerol pyrophosphate (DGPP), like DAG and lyso-phosphatidic acid (PA), is produced from PA via a single enzymatic step. Because all these lipids have been shown to potently mediate cellular signaling, we have examined the capacity of DGPP to mediate macrophage activation and the release of arachidonic acid (AA)-derived inflammatory mediators such as the eicosanoids
P388D1 macrophages were exposed to DGPP, an appreciable formation of prostaglandins such as PGE2 was detected in a dose- (Fig. 1A) and time-dependent (Fig. 1B) manner

Summary

Introduction

Leukocytes constitute the primary line of defense against infection. Recognition of foreign material by specific membrane receptors on the leukocyte surface enables these cells to mount an immunoinflammatory response that leads to killing of the microbe. We have found that the novel phospholipid diacylglycerol pyrophosphate (DGPP), identified in bacteria, yeast, and plants, but not in mammalian cells, is able to potently activate macrophages for enhanced secretion of arachidonate metabolites, a key event in the immunoinflammatory response of leukocytes.

Results

Conclusion