Nanoparticles enhance the ability of human neutrophils to exert phagocytosis by a Syk-dependent mechanism

Biochim Biophys Acta. 2015 Nov;1850(11):2276-82. doi: 10.1016/j.bbagen.2015.08.006. Epub 2015 Aug 13.


Background: Some reports indicate that NPs are ingested by cells via different mechanisms, including phagocytosis. In contrast, the direct role of NPs on the phagocytic process is not well documented. The aim of this study was to determine if titanium dioxide (TiO(2)), zinc oxide (ZnO) and cerium dioxide (CeO(2)) NPs, could alter the ability of neutrophils to exert phagocytosis.

Methods: Freshly isolated human neutrophils were incubated with NPs and their ability to phagocytose opsonized sheep red blood cells (SRBCs) or fluorescent latex beads (LBs) was assessed by optical and fluorescence microscopy, respectively. Syk activation was assessed by western blot experiments and a pharmacological approach with piceatannol, a Syk inhibitor, was used to determine its role in NPs-induced neutrophils. The cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) was used as a positive control.

Results: All tested NPs enhanced the ability of neutrophil to phagocytose SRBCs and LBs. Syk was activated in NPs-induced neutrophils as evidenced by its increased tyrosine phosphorylation level vs controls and the ability of NPs-induced phagocytosis was reversed by piceatannol.

Conclusions: We found that the tested NPs enhanced phagocytosis, although at different degree, and this occurred by a Syk-dependent mechanism.

General significance: This is the first study demonstrating that NPs, by themselves, can directly enhance FcR-mediated (opsonized SRBCs) and complement-mediated (LBs) phagocytosis. Moreover, as part of their mode of action, we determined that NPs can act similarly to GM-CSF leading to Syk activation involved in phagocytosis. This has to be taken under consideration for future nanobiology and nanomedicine studies.

Keywords: Nanobiology; Nanoparticles; Neutrophils; Phagocytosis; Syk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cerium / pharmacology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Metal Nanoparticles / administration & dosage*
  • Neutrophils / immunology*
  • Phagocytosis*
  • Protein-Tyrosine Kinases / physiology*
  • Syk Kinase
  • Titanium / pharmacology*
  • Zinc Oxide / pharmacology*


  • Intracellular Signaling Peptides and Proteins
  • titanium dioxide
  • Cerium
  • ceric oxide
  • Titanium
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • Zinc Oxide