β3-mediated engulfment of apoptotic tumor cells by dendritic cells is dependent on CAMKII: Inhibition by HIV-1 Tat

Alessandro Poggi, Roberta Carosio, Anna Rubartelli, Maria Raffaella Zocchi

Research output: Contribution to journalArticlepeer-review

Abstract

In this paper, we show that the engulfment of apoptotic tumor cells by DC requires the activation of the calcium-calmodulin kinase II (CAMKII). Indeed, DC phagocytosis of apoptotic lymphoma cells is consistently inhibited by KN62 and KN93, two blockers of CAMKII, but not by the inactive compound KN92. Wortmannin and LY294002, two inhibitors of the phosphatidyl-inositol-3 kinase, slightly decrease the phagocytosis of apoptotic cells, at variance with PD98059, an inhibitor of the mitogen-activated protein kinase. It is interesting that the addition of synthetic HIV-1 Tat, which we demonstrated to inhibit phagocytosis and calcium influx in DC, blocks the activation of CAMKII elicited via β3 integrin, which is involved in apoptotic body engulfment by DC. Experiments performed with Tat-derived peptides showed that this inhibition is mediated by the C-terminal domain of Tat. Finally, pertussis toxin can prevent HIV-1 Tat-mediated inhibition, suggesting the involvement of a guanosine triphosphate-binding (G) protein in DC-mediated phagocytosis.

Original languageEnglish
Pages (from-to)531-537
Number of pages7
JournalJournal of Leukocyte Biology
Volume71
Issue number3
Publication statusPublished - Mar 1 2002

Keywords

  • AIDS
  • Antigen-presenting cells
  • Calcium
  • G proteins
  • Phagocytosis

ASJC Scopus subject areas

  • Cell Biology

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