Inhibition of blood coagulation factor XIIIa‐mediated cross‐linking between fibronectin and collagen by polyamines

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Abstract
Soluble fibronectin is found in body fluids and media of cultured adherent cells. Insoluble fibronectin is found in tissue stroma and in extracellular matrices of cultured cells. Fibronectin is a substrate for factor XIIIa (plasma transglutaminase) and can be cross-linked to collagen and to the α chain of fibrin. We have used sodium dodecyl sulfate-polyacrylamide gel electrophoresis to investigate the possibility that factor XIIIa -mediated cross-linking is influenced by polyamines. Spermidine inhibited cross-linking between fibronectin and type I collagen, isolated α1 (I) collagen chains, or iodinated cyanogen bromide fragment 7 of α1 (I) chains (125I-α1 (I)-CB7). Half-maximal inhibition of crosslinking between 125I-α1 (I)-CB7 and fibronectin was observed when 0.1 mM spermine or spermidine was present. Spermidine, 0.7 mM, partially inhibited cross-linking between fibronectin and the α chain of fibrin but failed to inhibit cross-linking between the fibrin monomers of a fibrin clot. Spermidine also failed to inhibit cross-linking between fibronectin molecules when aggregation of fibronectin was induced with dithiothreitol. In contrast, 0.7 mM monodansylcadaverine inhibited fibronectin-collagen, fibronectin-fibrin, fibronectin-fibronectin, and fibrin-fibrin cross-linking. Spermidine or spermine, 0.7 mM, enhanced the cross-linking between molecules of partially amidinated fibronectin, suggesting that N1,8-(di-γ-glutamyl)-polyamine cross-linkages were formed. Spermidine and spermine failed to enhance cross-linking between monomers of amidinated fibrin. These results indicate that physiologic concentrations of polyamines specifically disturb transglutaminase-catalyzed cross-linking between fibronectin and collagen.