Thymosin β4 is released from human blood platelets and attached by factor XIIIa (transglutaminase) to fibrin and collagen

The beta-thymosins constitute a family of highly conserved and extremely water-soluble 5 kDa polypeptides. Thymosin beta(4) is the most abundant member; it is expressed in most cell types and is regarded as the main intracellular G-actin sequestering peptide. There is increasing evidence for extracellular functions of thymosin beta(4). For example, thymosin beta(4) increases the rate of attachment and spreading of endothelial cells on matrix components and stimulates the migration of human umbilical vein endothelial cells. Here we show that thymosin beta(4) can be cross-linked to proteins such as fibrin and collagen by tissue transglutaminase. Thymosin beta(4) is not cross-linked to many other proteins and its cross-linking to fibrin is competed by another family member, thymosin beta(10). After activation of human platelets with thrombin, thymosin beta(4) is released and crosslinked to fibrin in a time- and calcium-dependent manner. We suggest that thymosin beta(4) cross-linking is mediated by factor XIIIa, a transglutaminase that is coreleased from stimulated platelets. This provides a mechanism to increase the local concentration of thymosin beta(4) near sites of clots and tissue damage, where it may contribute to wound healing, angiogenesis and inflammatory responses.