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

  • Sci Rep. 2020 Jul 3;10(1):10976. doi: 10.1038/s41598-020-67345-3.
Mauro Valentino Paloschi  1  2 ,  Jéssica Amaral Lopes  1  2 ,  Charles Nunes Boeno  1  2 ,  Milena Daniela Souza Silva  1  2 ,  Jaína Rodrigues Evangelista  1 ,  Adriana Silva Pontes  1  2 ,  Sulamita da Silva Setúbal  1 ,  Cristina Matiele Alves Rego  1 ,  Neriane Monteiro Néry  1 ,  Alex Augusto Ferreira E Ferreira  1  2 ,  Weverson Luciano Pires  1 ,  Kátia Paula Felipin  3  2 ,  Gabriel Eduardo Melim Ferreira  3  2 ,  Patrícia Torres Bozza  4 ,  Juliana Pavan Zuliani  5  6  7
Affiliations
  • 1. Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, RO, Brazil.
  • 2. Programa de Pós-Graduação em Biologia Experimental, Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho, RO, Brazil.
  • 3. Laboratório de Epidemiologia Genética (EpiGen), Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, RO, Brazil.
  • 4. Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, IOC, Rio de Janeiro, RJ, Brazil.
  • 5. Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, RO, Brazil. [email protected].
  • 6. Centro de Estudos de Biomoléculas Aplicadas à Saúde (CEBio), Fundação Oswaldo Cruz, FIOCRUZ Rondônia e Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho, RO, Brazil. [email protected].
  • 7. Programa de Pós-Graduação em Biologia Experimental, Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho, RO, Brazil. [email protected].
PMID: 32620771 DOI: 10.1038/s41598-020-67345-3
Abstract

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 A2, mostly cytosolic Phospholipase A2-α (cPLA2-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 cPLA2-α, lipid droplet biogenesis and PGE2 synthesis were observed in human neutrophils stimulated with Cr-LAAO. Treatment with cPLA2-α inhibitor (CAY10650) or DGAT-1 inhibitor (A922500) suppressed lipid droplets formation and PGE2 secretion. In conclusion, we demonstrate for the first time the effects of Cr-LAAO to regulate neutrophil lipid metabolism and signalling.

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