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Hypoxia regulates human mast cell adhesion to fibronectin via the PI3K/AKT signaling pathway

Joanna Pastwińska1,2, Aurelia Walczak-Drzewiecka1, Magdalena Łukasiak1

  • 1Laboratory of Cellular Immunology, Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.

Cell Adhesion & Migration
|May 20, 2020
PubMed

Insights

Hypoxia, or low oxygen, enhances mast cell adhesion to fibronectin via the α5/β1 integrin receptor. This process, regulated by PI3K/Akt signaling, may guide mast cells to inflammatory sites.

Area of Science:

  • Immunology
  • Cell Biology
  • Physiology

Background:

  • Inflammatory reactions are often characterized by decreased oxygen levels (hypoxia).
  • Mast cells are key immune cells involved in inflammation and interact with their environment via adhesion receptors.
  • Integrins are crucial adhesion receptors mediating cell-matrix interactions.

Purpose of the Study:

  • To investigate the effect of hypoxia on integrin-mediated mast cell adhesion to fibronectin.
  • To elucidate the specific integrin receptor and signaling pathways involved.

Main Methods:

  • Mast cell adhesion assays were performed under normoxic and hypoxic conditions.
  • Surface expression of integrins was analyzed.
  • Western blotting was used to assess protein phosphorylation (Akt).
  • The role of PI3K signaling was examined using specific inhibitors.

Main Results:

  • Hypoxia significantly upregulated mast cell adhesion to fibronectin, mediated by the α5/β1 integrin receptor.
  • This upregulation occurred without changes in surface integrin expression, indicating regulation via inside-out signaling.
  • Hypoxia increased Akt phosphorylation in a manner dependent on PI3K activity.
  • PI3K inhibitors abolished the hypoxia-induced increase in mast cell adhesion.

Conclusions:

  • Hypoxia enhances mast cell adhesion to fibronectin through PI3K/Akt-dependent inside-out signaling.
  • The α5/β1 integrin receptor is critical for this hypoxia-mediated adhesion.
  • This mechanism may play a significant role in directing mast cell localization to inflammatory sites.
Keywords:
AKTLAD2Mast cellsPI3KSCFadhesionfibronectinhypoxiaintegrin α5β1wortmannin

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