Functional thrombin receptors on human T lymphoblastoid cells

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Thrombin is a key enzyme in coagulation.
• Its role in immune cell activation is not fully understood.
• T cells and B cells exhibit distinct responses to various stimuli.

Purpose of the Study:

• To investigate the effect of human alpha-thrombin on T and B lymphoblastoid cell lines.
• To identify the presence and function of thrombin receptors on T cells.
• To explore thrombin's potential role in T cell activation independent of the immune response.

Main Methods:

• Stimulation of T and B cell lines with alpha-thrombin.
• Measurement of intracellular free Ca2+ concentrations.
• Assay of inositol trisphosphate liberation and protein kinase C activation.
• Use of thrombin inhibitors (hirudin) and receptor-activation peptides.
• Flow-cytometric analysis using monoclonal antibodies (mAbs) against the thrombin receptor.

Main Results:

• Alpha-thrombin increased intracellular free Ca2+ in T cells but not B cells.
• Thrombin-induced responses involved rapid calcium flux, inositol trisphosphate liberation, and protein kinase C activation.
• Hirudin blocked alpha-thrombin's effect, while thrombin receptor-activation peptides stimulated T cells.
• Flow cytometry confirmed thrombin receptor presence on T cells, absent on B cells.
• Cross-desensitization occurred between alpha-thrombin and its receptor-activation peptide, but not with TCR/CD3 activation.

Conclusions:

• Functional thrombin receptors are present on T lymphoblastoid cells.
• Thrombin can activate T cells through these receptors, independent of B cell activation.
• This activation pathway may play a role in T cell function outside of traditional immune responses.