P2X7 receptor activation increases expression of caveolin-1 and formation of macrophage lipid rafts, thereby boosting CD39 activity

Research output: Contribution to journalArticle

Authors

  • Luiz Eduardo Baggio Savio
  • Paola De Andrade Mello
  • Stephanie Alexia Cristina Silva Santos
  • Júlia Costa De Sousa
  • Suellen D.S. Oliveira
  • Richard D. Minshall
  • Eleonora Kurtenbach
  • Yan Wu
  • Maria Serena Longhi
  • Simon C. Robson
  • Robson Coutinho-Silva

External Institution(s)

  • Universidade Federal do Rio de Janeiro
  • Harvard University
  • University of Illinois at Chicago

Details

Original languageEnglish (US)
Article numberjcs237560
JournalJournal of cell science
Volume133
Issue number5
StatusPublished - Mar 2020
Peer-reviewedYes

Abstract

Macrophages are tissue-resident immune cells that are crucial for the initiation and maintenance of immune responses. Purinergic signaling modulates macrophage activity and impacts cellular plasticity. The ATP-activated purinergic receptor P2X7 (also known as P2RX7) has pro-inflammatory properties, which contribute to macrophage activation. P2X7 receptor signaling is, in turn, modulated by ectonucleotidases, such as CD39 (also known as ENTPD1), expressed in caveolae and lipid rafts. Here, we examined P2X7 receptor activity and determined impacts on ectonucleotidase localization and function in macrophages primed with lipopolysaccharide (LPS). First, we verified that ATP boosts CD39 activity and caveolin-1 protein expression in LPS-primed macrophages. Drugs that disrupt cholesterol-enriched domains - such as nystatin and methyl-β-cyclodextrin - decreased CD39 enzymatic activity in all circumstances. We noted that CD39 colocalized with lipid raft markers (flotillin-2 and caveolin-1) in macrophages that had been primed with LPS followed by treatment with ATP. P2X7 receptor inhibition blocked these ATP-mediated increases in caveolin-1 expression and inhibited the colocalization with CD39. Further, we found that STAT3 activation is significantly attenuated caveolin-1-deficient macrophages treated with LPS or LPS+BzATP. Taken together, our data suggest that P2X7 receptor triggers the initiation of lipid raft-dependent mechanisms that upregulates CD39 activity and could contribute to limit macrophage responses restoring homeostasis.

    Research areas

  • Ectonucleotidases, Extracellular ATP, Lipid rafts, Macrophages, P2RX7, Purinergic signaling

Citation formats

APA

Savio, L. E. B., De Andrade Mello, P., Santos, S. A. C. S., De Sousa, J. C., Oliveira, S. D. S., Minshall, R. D., ... Coutinho-Silva, R. (2020). P2X7 receptor activation increases expression of caveolin-1 and formation of macrophage lipid rafts, thereby boosting CD39 activity. Journal of cell science, 133(5), [jcs237560]. https://doi.org/10.1242/JCS.237560

Harvard

Savio, LEB, De Andrade Mello, P, Santos, SACS, De Sousa, JC, Oliveira, SDS, Minshall, RD, Kurtenbach, E, Wu, Y, Longhi, MS, Robson, SC & Coutinho-Silva, R 2020, 'P2X7 receptor activation increases expression of caveolin-1 and formation of macrophage lipid rafts, thereby boosting CD39 activity', Journal of cell science, vol. 133, no. 5, jcs237560. https://doi.org/10.1242/JCS.237560