Development of a novel, cell-based chemical screen to identify inhibitors of intraphagosomal lipolysis in macrophages Academic Article uri icon

Overview

MeSH Major

  • High-Throughput Screening Assays
  • Lipolysis
  • Macrophages
  • Phagosomes
  • Small Molecule Libraries

abstract

  • Macrophages play a central role in tissue homeostasis and the immune system. Their primary function is to internalize cellular debris and microorganisms for degradation within their phagosomes. In this context, their capacity to process and sequester lipids such as triacylglycerides and cholesteryl esters makes them key players in circulatory diseases, such as atheroclerosis. To discover new inhibitors of lipolytic processing within the phagosomal system of the macrophage, we have developed a novel, cell-based assay suitable for high-throughput screening. We employed particles carrying a fluorogenic triglyceride substrate and a calibration fluor to screen for inhibitors of phagosomal lipolysis. A panel of secondary assays were employed to discriminate between lipase inhibitors and compounds that perturbed general phagosomal trafficking events. This process enabled us to identify a new structural class of pyrazole-methanone compounds that directly inhibit lysosomal and lipoprotein lipase activity.

publication date

  • August 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2909615

Digital Object Identifier (DOI)

  • 10.1002/cyto.a.20911

PubMed ID

  • 20653015

Additional Document Info

start page

  • 751

end page

  • 60

volume

  • 77

number

  • 8