Can phage display be used as a tool to functionally identify endogenous eat-me signals in phagocytosis?

Nora B. Caberoy, Yixiong Zhou, Wei Li

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Removal of apoptotic cells and cellular debris by phagocytosis is essential for development, tissue homeostasis, and resolution of inflammation. Eat-me signals control the initiation of phagocytosis, holding a key to the understanding of phagocyte biology. Because of a lack of functional cloning strategy, eat-me signals are conventionally identified and characterized on a case-by-case basis. The feasibility of functional cloning of eat-me signals by phage display is investigated by characterizing the biological behavior of T7 phages displaying 2 well-known eat-me signals: growth arrest-specific gene 6 (Gas6) and milk fat globule-EGF8 (MFG-E8). Gas6-phage binds to all 3 known Gas6 receptors: Mer, Axl, and Tyro3 receptor tyrosine kinases. Gas6-phage and MFG-E8-phage are capable of binding to phagocytes and nonphagocytes. However, both phages stimulate phage uptake only in phagocytes, including macrophages, microglia, and retinal pigment epithelium cells, but not in nonphagocytes. Furthermore, functional phage selection by phagocytosis in phagocytes enriches both Gas6-phage and MFG-E8-phage, suggesting that phage display can be used as a tool to functionally identify unknown eat-me signals from phage display cDNA library.

Original languageEnglish (US)
Pages (from-to)653-661
Number of pages9
JournalJournal of Biomolecular Screening
Volume14
Issue number6
DOIs
StatePublished - Jul 2009

Keywords

  • Eat-me signals
  • Gas6
  • MFG-E8
  • Phage display
  • Phagocytosis

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmacology
  • Biochemistry
  • Molecular Medicine
  • Biotechnology

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