Interferon-γ stimulates p11-dependent surface expression of annexin A2 in lung epithelial cells to enhance phagocytosis

Yi Ting Fang, Chiou Feng Lin, Chi Yun Wang, Robert Anderson, Yee Shin Lin

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Annexin A2 (p36) is usually present together with its natural ligand p11 as a heterotetramer complex, which has multiple biological functions depending on its cellular localization. However, the detailed mechanism of annexin A2 translocation and its physiological role in inflammation remain unclear. Here, we show that IFN-γ stimulation enhances surface translocation of annexin A2 on lung epithelial cells. While total annexin A2 protein remains unchanged, the expression of p11 is upregulated via the IFN-γ-activated JAK2/STAT1 signal pathway. Notably, IFN-γ-induced p11 expression is required for annexin A2 translocation to the cell surface. Since annexin A2 lacks a signal peptide for surface translocation by the classical endoplasmic reticulum-Golgi route, its mode of trafficking remains unclear. We observed that p11-dependent surface translocation of annexin A2 is associated with the exosomal secretion pathway. The IFN-γ-induced increase of annexin A2 in the exosomes is blocked in p11-silenced cells. Furthermore, IFN-γ-induced surface expression of annexin A2 mediates phagocytosis of apoptotic cells by lung epithelial cells. These findings provide insights into the surface translocation mechanism of annexin A2 and illustrate a pivotal function of surface annexin A2 in the phagocytic response to IFN-γ.

Original languageEnglish
Pages (from-to)2775-2787
Number of pages13
JournalJournal of Cellular Physiology
Volume227
Issue number6
DOIs
Publication statusPublished - Jun 2012
Externally publishedYes

Fingerprint

Annexin A2
Phagocytosis
Interferons
Epithelial Cells
Lung
Exosomes
Cytophagocytosis
Secretory Pathway
Protein Sorting Signals
Endoplasmic Reticulum
Signal Transduction

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Interferon-γ stimulates p11-dependent surface expression of annexin A2 in lung epithelial cells to enhance phagocytosis. / Fang, Yi Ting; Lin, Chiou Feng; Wang, Chi Yun; Anderson, Robert; Lin, Yee Shin.

In: Journal of Cellular Physiology, Vol. 227, No. 6, 06.2012, p. 2775-2787.

Research output: Contribution to journalArticle

Fang, Yi Ting ; Lin, Chiou Feng ; Wang, Chi Yun ; Anderson, Robert ; Lin, Yee Shin. / Interferon-γ stimulates p11-dependent surface expression of annexin A2 in lung epithelial cells to enhance phagocytosis. In: Journal of Cellular Physiology. 2012 ; Vol. 227, No. 6. pp. 2775-2787.
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