Related Experiment Videos
Lymphocyte adhesion mediated by lymphocyte function-associated antigen-1. II. Interaction between phorbol ester- and
1Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908.
Journal of Immunology (Baltimore, Md. : 1950)
|July 15, 1992
Summary
Lymphocyte adhesion, mediated by LFA-1 and ICAM-1, is regulated by protein kinases C and A. These kinases interact sequentially to control adhesion, with protein kinase C mediating early adhesion and protein kinase A influencing later stages.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Lymphocyte adhesion is crucial for immune responses.
- Lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) mediate cell adhesion.
- Protein kinases C (PKC) and A (PKA) are key signaling molecules in cellular processes.
Purpose of the Study:
- To investigate the roles of PKC and PKA in regulating LFA-1/ICAM-1-mediated lymphocyte adhesion.
- To elucidate the temporal dynamics of adhesion regulation by these kinases.
Main Methods:
- Treatment of JY cells with phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS).
- Manipulation of intracellular cAMP levels to activate PKA.
- Use of specific kinase inhibitors to dissect signaling pathways.
Main Results:
- PMA induced rapid LFA-1 capping and adhesion, inhibited by elevated cAMP (PKA activation).
- LPS induced biphasic adhesion, with an early PKC-dependent phase and a later PKA-influenced phase.
- PKC inhibition abrogated early LPS-induced adhesion, while PKA inhibition attenuated late adhesion.
Conclusions:
- Lymphocyte adhesion is regulated by a complex interplay between PKC and PKA.
- A model of sequential induction, inhibition, and reinduction of adhesion is proposed, driven by temporally ordered kinase activity.
- Kinase signaling pathways provide a mechanism for fine-tuning immune cell interactions.