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The serine protease cofactor factor V is synthesized by lymphocytes
1Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Journal of Immunology (Baltimore, Md. : 1950)
|April 1, 1993
Summary
Human lymphocytes can produce factor V, a key protein in blood clotting. This finding reveals a new role for lymphocytes in immune responses and inflammation at sites outside blood vessels.
Area of Science:
- Immunology
- Hematology
- Molecular Biology
Background:
- Cellular immune responses activate CD4+ T cells, leading to tissue factor expression and coagulation cascade initiation.
- Thrombin, generated by the coagulation cascade, influences cellular responses and fibrin deposition.
- The role of extravascular cells in immune effector pathways, particularly in providing coagulation cofactors, was unclear.
Purpose of the Study:
- To investigate the potential for extravascular cells, specifically lymphocytes, to provide the cofactor factor Va.
- To determine if lymphocytes transcribe and synthesize factor V, a crucial component of the coagulation cascade.
Main Methods:
- Reverse transcription followed by polymerase chain reaction (RT-PCR) to detect Factor V mRNA in human lymphoid cells.
- Cloning of factor V cDNA from a T cell cDNA library for confirmation.
- Northern blot analysis to confirm the presence and abundance of factor V mRNA in T cell lines and lymphocytes.
- Immunocytology using a factor V monoclonal antibody (mAb) to detect intracellular factor V protein.
Main Results:
- Factor V mRNA was detected in human lymphoid cells, including T lymphoma cell lines, unstimulated lymphocytes, and stimulated T cells.
- Factor V cDNA cloned from a T cell library showed high sequence similarity to hepatic factor V mRNA.
- Northern blot confirmed a approximately 7-kb factor V mRNA transcript in T cells.
- Immunocytology revealed intracellular, but not surface, factor V in T lymphocytes.
Conclusions:
- Human lymphocytes are capable of transcribing and synthesizing factor V.
- Lymphocytes can provide essential cofactors for the coagulation cascade at extravascular sites.
- This discovery offers a new perspective on the contribution of lymphocytes to inflammatory and immune effector functions.