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Updated: Jan 20, 2026
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Functional Assessment of Intestinal Permeability and Neutrophil Transepithelial Migration in Mice using a Standardized Intestinal Loop Model
Published on: February 11, 2021
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A Negative Feedback Loop Regulates Integrin Inactivation and Promotes Neutrophil Recruitment to Inflammatory Sites.
Barry McCormick1, Helen E Craig2, Julia Y Chu1
1Centre for Inflammation Research, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
Journal of Immunology (Baltimore, Md. : 1950)
|August 21, 2019
Summary
The GTPase activating protein ARAP3 is crucial for integrin inactivation in neutrophils. ARAP3 regulates a negative feedback loop, controlling neutrophil recruitment to inflammation sites.
Area of Science:
- Cellular Biology
- Immunology
- Molecular Biology
Background:
- Neutrophil recruitment to inflammation sites is integrin-dependent.
- Mechanisms regulating integrin inactivation are poorly understood.
- Integrin activation is well-characterized, but inactivation is not.
Purpose of the Study:
- To investigate the role of ARAP3 in integrin inactivation.
- To elucidate the molecular mechanisms of integrin inactivation.
- To understand ARAP3's function in neutrophil migration and recruitment.
Main Methods:
- Utilized mouse neutrophils and Chinese hamster ovary cells.
- Investigated ARAP3's role in a negative feedback loop downstream of PI3K.
- Analyzed in vitro neutrophil functions (PIP3 polarization, adhesion turnover, transendothelial migration).
- Assessed in vivo neutrophil recruitment to inflammatory sites.
Main Results:
- ARAP3 is a critical regulator of integrin inactivation.
- ARAP3 functions in a negative feedback loop downstream of PI3K.
- ARAP3 promotes localized integrin inactivation and adhesion turnover.
- ARAP3-deficient neutrophils exhibit defective migration and recruitment.
- ARAP3 deficiency causes neutrophil-autonomous recruitment defects.
Conclusions:
- ARAP3 is essential for integrin inactivation in neutrophils and other cells.
- ARAP3 regulates integrin-mediated PI3K activity via negative feedback.
- ARAP3 plays a vital role in neutrophil recruitment to inflammatory sites.
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