Alternative pathways for the activation of factor XIII

Area of Science:

• Biochemistry
• Hematology
• Molecular Biology

Background:

• Factor XIII (FXIII) is a plasma proenzyme crucial for fibrin stabilization.
• FXIII activation catalyzes the formation of epsilon(gamma-glutamyl)lysyl bonds in fibrin, crosslinking the clot.
• Understanding FXIII activation pathways is vital for comprehending blood coagulation and thrombosis.

Purpose of the Study:

• To quantitatively assess the activation of purified plasma Factor XIII by various serine proteases.
• To investigate the role of calcium in Factor XIII activation by different enzymes.
• To explore potential alternative pathways for Factor XIII activation in vivo.

Main Methods:

• Purified plasma Factor XIII was activated using thrombin, trypsin, chymotrypsin, factor Xa, and Reptilase.
• The fluorescent amine incorporation assay was employed for quantitative activation analysis.
• Polyacrylamide gel electrophoresis was used to examine activation products.

Main Results:

• Highly purified thrombin and trypsin effectively activated Factor XIII, independent of calcium.
• Factor Xa also activated Factor XIII, but this process was calcium-dependent.
• Chymotrypsin did not exhibit transglutaminase activity on Factor XIII.
• Reptilase activity was attributed to contaminating enzymes in less purified preparations.

Conclusions:

• Factor Xa can activate Factor XIII, potentially forming Factor XIIIa via an alternative pathway in vivo.
• Factor XIIIa formation by Factor Xa could contribute to alternative thrombus formation pathways.
• Dual activation of Factor XIII by thrombin and Factor Xa offers additional regulatory control points in blood coagulation.