Cytosolic phospholipase A2-α participates in lipid body formation and PGE2 release in human neutrophils stimulated with an l-amino acid oxidase from Calloselasma rhodostoma venom

• Published in: Scientific reports 2020-07, Vol.10 (1), Article 10976
• Main Authors: Paloschi, Mauro Valentino, Lopes, Jéssica Amaral, Boeno, Charles Nunes, Silva, Milena Daniela Souza, Evangelista, Jaína Rodrigues, Pontes, Adriana Silva, da Silva Setúbal, Sulamita, Rego, Cristina Matiele Alves, Néry, Neriane Monteiro, Ferreira e Ferreira, Alex Augusto, Pires, Weverson Luciano, Felipin, Kátia Paula, Ferreira, Gabriel Eduardo Melim, Bozza, Patrícia Torres, Zuliani, Juliana Pavan
• Format: Article
• Language: English
• Subjects: 631/250/2504; 631/250/256; Acyltransferase; Amino acid oxidase; Amino acids; Biosynthesis; Cell activation; Cyclooxygenase-2; Diacylglycerol O-acyltransferase; Diglycerides; Humanities and Social Sciences; Inflammation; Leukocytes (neutrophilic); Lipid metabolism; Lipids; Metabolism; multidisciplinary; Neutrophils; Phospholipase A2; Phosphorylation; Prostaglandin E; Prostaglandin E2; Science; Science (multidisciplinary); Venom
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-67345-3

Cr-LAAO, an l -amino acid oxidase isolated from Calloselasma rhodosthoma snake venom, has been demonstrated as a potent stimulus for neutrophil activation and inflammatory mediator production. However, the mechanisms involved in Cr-LAAO induced neutrophil activation has not been well characterized. Here we investigated the mechanisms involved in Cr-LAAO-induced lipid body (also known as lipid droplet) biogenesis and eicosanoid formation in human neutrophils. Using microarray analysis, we show for the first time that Cr-LAAO plays a role in the up-regulation of the expression of genes involved in lipid signalling and metabolism. Those include different members of phospholipase A 2, mostly cytosolic phospholipase A 2 -α (cPLA 2 -α); and enzymes involved in prostaglandin synthesis including cyclooxygenases 2 (COX-2), and prostaglandin E synthase (PTGES). In addition, genes involved in lipid droplet formation, including perilipin 2 and 3 (PLIN 2 and 3) and diacylglycerol acyltransferase 1 (DGAT1), were also upregulated. Furthermore, increased phosphorylation of cPLA 2 -α, lipid droplet biogenesis and PGE 2 synthesis were observed in human neutrophils stimulated with Cr-LAAO. Treatment with cPLA 2 -α inhibitor (CAY10650) or DGAT-1 inhibitor (A922500) suppressed lipid droplets formation and PGE 2 secretion. In conclusion, we demonstrate for the first time the effects of Cr-LAAO to regulate neutrophil lipid metabolism and signalling.