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Human T Lymphocyte Isolation, Culture and Analysis of Migration In Vitro
Published on: June 2, 2010
The affinity of integrin alpha(4)beta(1) governs lymphocyte migration
D M Rose1, V Grabovsky, R Alon
1Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|August 18, 2001
Summary
Integrin alpha(4)beta(1) activation is crucial for lymphocyte trafficking. Defective activation significantly impairs alpha(L)beta(2)-dependent cell migration, highlighting its role in immune cell homing.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Integrin alpha(4)beta(1) interaction with VCAM-1 mediates lymphocyte trafficking from blood to tissues.
- Leukocyte trafficking is tightly regulated by cellular control over integrin affinity, termed activation.
- Understanding the functional significance of alpha(4)beta(1) activation is key to deciphering immune cell homing mechanisms.
Purpose of the Study:
- To investigate the biological role of alpha(4)beta(1) integrin activation in cell migration.
- To determine how defects in alpha(4)beta(1) activation affect VCAM-1-mediated cell trafficking.
- To elucidate the threshold set by alpha(4)beta(1) activation for VCAM-1-dependent migration.
Main Methods:
- Isolation of Jurkat T cell lines with impaired alpha(4)beta(1) activation.
- Assessment of alpha(L)beta(2)-dependent cell migration on VCAM-1.
- Utilizing activating antibodies to rescue alpha(4)beta(1) function.
Main Results:
- Cells with defective alpha(4)beta(1) activation showed a 20-fold increase in VCAM-1 requirement for alpha(L)beta(2)-dependent migration.
- An activating antibody restored alpha(4)beta(1)-stimulated alpha(L)beta(2)-dependent migration, confirming the defect was in affinity.
- Migration on VCAM-1 alone was enhanced at higher densities in activation-defective cells.
Conclusions:
- Alpha(4)beta(1) activation establishes a critical threshold for VCAM-1 to regulate both alpha(L)beta(2) and alpha(4)beta(1)-dependent cell migration.
- This activation threshold influences the anatomical sites of leukocyte emigration.
- Proper alpha(4)beta(1) activation is essential for efficient and specific immune cell homing.
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01:19Cell Migration
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