In Vitro Models of Phagocytosis and Efferocytosis in THP-1 Cells

Compound Screening by HCI in Unique Model of Efferocytosis and Phagocytosis

Aberrations in efferocytosis are associated with numerous inflammatory pathologies, including cancer, atherosclerosis, and infections. Phenotypic screening of compounds around either of these mechanisms can now be achieved in partnership with Eurofins Integrated Discovery.
 
Phagocytosis and efferocytosis are both processes by which phagocytes recognize and engulf foreign material to remove it. Phagocytosis is often the first line of defense against microbes and will still trigger an inflammatory response, while efferocytosis is associated with apoptosis and the engulfment of apoptotic cells and the release of an anti-inflammatory signal. Although most cells are capable of phagocytosis, some cell types perform it as part of their main function. These are called “professional phagocytes” and include neutrophils, macrophages, monocytes, dendritic cells, osteoclasts, and eosinophils.
 
Utilize the human monocytic cell line, THP-1 (differentiated into a macrophage phenotype), as a model of both phagocytosis and efferocytosis. Eurofins Discovery exclusively provides an efferocytosis assay and offers the corresponding phagocytosis assay in the same cell type. A pHrodo Green E Coli Bioparticles conjugate triggers phagocytosis, and apoptotic human neuroblastoma SH-SY5Y labeled with a fluorescent marker is used for the efferocytosis model. These models can be run together or in isolation.

  • 96-well format
  • 8-point concentration range to generate an EC50 or as single concentration for library screening
  • High-content imaging readout
  • Under development: ioMicroglia in place of THP-1 cells

 

Phagocytosis

 
Phagocytosis

↑ Pro-inflammatory signaling

 

  1. Binding & Absorption
  2. Phagosome Formation
  3. Phagolysosome formation
  4. Digestion
  5. Exocytosis
Efferocytosis

 
Efferocytosis

↑ Anti-inflammatory signaling

 

  1. “Find me” signal on apoptotic cell recruit macrophages
  2. “Eat me” signal triggers engulfment
  3. Phagosome formation
  4. LC3 recruited to phagosome to form LaPosome
  5. Lysosome mediated digestion → ↑ Fatty Acids

Features