New insights into the expression and role of platelet factor XIII-A

Summary. Background: The A subunit of factor XIII (FXIII-A) functions as an intracellular transglutaminase (TG) in themegakaryocyte/platelet lineage, where it probably participatesin the cytoskeletal remodeling associated with cell activation.However,sofar,thepreciseroleofcellularFXIII(cFXIII)andthe functionalconsequences ofits absencein FXIII-A-deficientpatientsareunknown. Objectivesandmethods: Inthisstudy,weused platelets from four patients with congenital deficiency ofFXIII-A to study the role of cFXIII in platelet functions.Results: We found that FXIII-A represents the only detectablesource of TG activity in platelets and that the binding offibrinogen in response to thrombin receptor agonist peptide(TRAP) stimulation was significantly reduced in platelets fromthe patients. In agreement with this, in control platelets,monodansyl-cadaverine (MDC), a competitive amino-donorfor TGs, inhibited fibrinogen binding induced by TRAP in adose-dependent manner. Moreover, upon adhesion to fibrino-gen,normalplateletsincubated withMDCaswellas FXIII-A-deficient platelets showed a distinct extension pattern withreduced lamellipodia and increased filopodia formation, sug-gesting a delay in spreading. Conclusions: These findingsprovide evidence for the direct involvement of cFXIII-depen-dent TG activity in the regulation of platelet functions.Keywords: FXIII-A, platelet activation, transglutaminaseactivity.IntroductionBlood coagulation factor XIII (FXIII) is a plasma transgluta-minase (TG) that circulates as a heterotetramer composed oftwo catalytic A subunits and two non-catalytic B subunits(A