Abstract
A decrease in oxygen concentration is a hallmark of inflammatory reactions resulting from infection or homeostasis disorders. Mast cells interact with extracellular matrix and other cells by adhesion receptors. We investigated the effect of hypoxia on integrin-mediated mast cell adhesion to fibronectin. We found that it was mediated by the α5/β1 receptor and that hypoxia significantly upregulated this process. Hypoxia-mediated increases in mast cell adhesion occurred without increased surface expression of integrins, suggesting regulation by inside-out integrin signaling. Hypoxia also mediated an increase in phosphorylation of Akt, and PI3'kinase inhibitors abolished hypoxia-mediated mast cell adhesion. Hypoxia upregulates the function of integrin receptors by PI3' kinase-dependent signaling. This process might be important for the location of mast cells at inflammatory sites.
Keywords:
AKT; LAD2; Mast cells; PI3K; SCF; adhesion; fibronectin; hypoxia; integrin α5β1; wortmannin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Adhesion / drug effects
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Cell Hypoxia / drug effects
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Cell Line
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Fibronectins / pharmacology*
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Humans
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Integrin alpha5beta1 / metabolism
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Mast Cells / cytology*
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Mast Cells / drug effects
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Mast Cells / enzymology*
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Oligopeptides / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphatidylinositol 3-Kinases / pharmacology
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Phosphoinositide-3 Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / pharmacology
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Proto-Oncogene Proteins c-akt / metabolism*
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Receptors, Cell Surface / metabolism
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Signal Transduction* / drug effects
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Stem Cell Factor / pharmacology
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Wortmannin / pharmacology
Substances
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Fibronectins
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Integrin alpha5beta1
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Oligopeptides
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors
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Receptors, Cell Surface
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Stem Cell Factor
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arginyl-glycyl-aspartic acid
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Proto-Oncogene Proteins c-akt
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Wortmannin
Grants and funding
This work was supported by the National Science Centre grant no. 2015/17/B/NZ6/04252.