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Beta1-integrins mediate Ca2+-signalling and T cell spreading via divergent pathways
H Schöttelndreier1, G W Mayr, A H Guse
1University of Hamburg, Institute of Physiological Chemistry, Department of Enzyme Chemistry, Germany.
Cellular Signalling
|August 5, 1999
Summary
Jurkat T-lymphocytes adhere strongly to extracellular matrix proteins like laminin and collagen type IV when combined with poly-L-lysine. This interaction triggers calcium signaling and cell spreading via distinct pathways.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Extracellular matrix (ECM) proteins, such as laminin and collagen type IV, play crucial roles in cell adhesion and signaling.
- T-lymphocytes interact with ECM components, influencing their function and behavior.
- Understanding these interactions is vital for fields like immunology and regenerative medicine.
Purpose of the Study:
- To investigate the effects of combining basement membrane ECM proteins (laminin, collagen type IV) with poly-L-lysine on Jurkat T-lymphocyte adhesion, calcium signaling, and cell spreading.
- To elucidate the distinct signal transduction pathways involved in T-lymphocyte adhesion, calcium signaling, and spreading mediated by ECM proteins and poly-L-lysine.
Main Methods:
- Jurkat T-lymphocytes were cultured on surfaces coated with laminin or collagen type IV alone, or in combination with poly-L-lysine.
- Cell adhesion, intracellular calcium concentration ([Ca2+]i) changes, and cell spreading were measured.
- Specific inhibitors targeting key enzymes (tyrosine kinase, PKC, PLCgamma, PLA2) and antibodies (anti-beta1 mAb) were used to block signaling pathways.
Main Results:
- Poly-L-lysine combined with ECM proteins induced strong adhesion, increased [Ca2+]i, and cell spreading, unlike ECM proteins alone.
- Adhesion to poly-L-lysine was charge-dependent and independent of beta1-integrin and [Ca2+]i increase.
- Anti-beta1 mAb blocked Ca2+ signaling and spreading on ECM proteins combined with poly-L-lysine.
- Tyrosine kinase inhibitors blocked both Ca2+ signaling and spreading, while PKC, PLCgamma, and PLA2 inhibitors selectively blocked spreading.
Conclusions:
- T-lymphocyte interaction with ECM proteins and poly-L-lysine involves distinct pathways for adhesion, calcium signaling, and spreading.
- Charge-based interactions mediate strong adhesion, while beta1-integrin and calcium signaling are involved in ECM-mediated responses.
- Divergent intracellular signaling cascades regulate T-lymphocyte spreading and calcium responses upon interaction with ECM components.