Summary
The potentially active A subunit of factor XIII of blood coagulation has also been
detected in platelets and monocytes/macrophages though the exact function of this
cellular protransglutaminase has not yet been elucidated. In physiological conditions
the first step in the activation of plasma factor XIII is the removal of an activation
peptide from the N-terminal end of subunit A by thrombin. The A subunit then, in the
presence of Ca2+, dissociates from the inhibitory B subunit and assumes an active conformation. Cellular
factor XIII, which lacks B subunit, can be proteolytically activated in vitro by thrombin
and the intracellular Ca2+ sensitive protease, calpain, in the same way as plasma factor XIII subunit A, and
calpain has been suggested as the intracellular protease involved in the activation
of cellular factor XIII in platelets. In the present experiments it was shown by SDS
PAGE that during long-term stimulation of platelets with thrombin nondisulfide-crosslinked
high M
r protein polymers not penetrating the concentrating gel were formed. The lack of these
polymers in thrombin-stimulated factor XIII deficient platelets clearly indicated
that their formation in normal platelets was due to factor XIII that became active
during platelet activation. However, no release of the activation peptide could be
detected by Western blotting during this process. Similarly, no proteolytic cleavage
of factor XIII was detectable when platelets were stimulated by Ca2+ ionophore through this stimulus activated calpain as it was clearly demonstrated
by the breakdown of major intracellular calpain substrates. The results indicate:
1) during thrombin induced platelet activation factor XIII becomes active and crosslinks
platelet protein, 2) platelet factor XIII is not an intracellular substrate of calpain,
3) cellular factor XIII could be activated without the proteolytic removal of activation
peptide. It is presumed that the nonproteolytic pathway for the activation of cellular
factor XIII, we reported most recently, might have physiological implications under
such conditions.
