Abstract
Adrenic acid (AA), the 2-carbon elongation product of arachidonic acid, is present at significant levels in membrane phospholipids of mouse peritoneal macrophages. Despite its abundance and structural similarity to arachidonic acid, very little is known about the molecular mechanisms governing adrenic acid mobilization in cells of the innate immune system. This contrasts with the wide availability of data on arachidonic acid mobilization. In this work, we used mass-spectrometry-based lipidomic procedures to define the profiles of macrophage phospholipids that contain adrenic acid and their behavior during receptor activation. We identified the phospholipid sources from which adrenic acid is mobilized, and compared the data with arachidonic acid mobilization. Taking advantage of the use of selective inhibitors, we also showed that cytosolic group IVA phospholipase A2 is involved in the release of both adrenic and arachidonic acids. Importantly, calcium independent group VIA phospholipase A2 spared arachidonate-containing phospholipids and hydrolyzed only those that contain adrenic acid. These results identify separate mechanisms for regulating the utilization of adrenic and arachidonic acids, and suggest that the two fatty acids may serve non-redundant functions in cells.
Highlights
Arachidonic acid (cis-5,8,11,14-eicosatetraenoic acid, Adrenic acid (AA)), a fatty acid of the n-6 series, is the major polyunsaturated fatty acid present in cells of the innate immunity [1]
Arachidonic acid, a fatty acid of the n-6 series, is the major polyunsaturated fatty acid present in cells of the innate immunity [1]
Lipid extracts from mouse peritoneal macrophages were analyzed for fatty acid content by GC/MLiSp.idToextatrlaActAs fcroonmtemnot uwsaesp6e9ri.9to±ne4a.2l mnmacorol/pmhgagceesllwperroeteainnal(ymzeeadnfovraflautetys a±csidtacnodnatredntebrryoGr Cof/MthSe
Summary
Arachidonic acid (cis-5,8,11,14-eicosatetraenoic acid, AA), a fatty acid of the n-6 series, is the major polyunsaturated fatty acid present in cells of the innate immunity [1]. Cleavage of AA-containing membrane phospholipids by phospholipase A2 (PLA2) enzymes during activation results in substantial release of free AA. Innate immune cells contain significant quantities of another n-6 fatty acid, adrenic acid (cis-7,10,13,16-docosatetraenoic acid, AdA), which is the 2-carbon elongation product of AA [1]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have