Effect of factor XIII on endothelial barrier function

The effect of factor XIII on endothelial barrier function was studied in a model of cultured monolayers of porcine aortic endothelial cells and saline -perfused rat hearts. The thrombin-activated plasma factor XIII (1 U/ml) re duced albumin permeability of endothelial monolayers within 20 min by 30 +/ - 7% (basal value of 5.9 +/- 0.4 x 10(-6) cm/s), whereas the nonactivated p lasma factor XIII had no effect. Reduction of permeability to the same exte nt, i.e., by 34 +/- 9% could be obtained with the thrombin-activated A subu nit of factor XIII (1 U/ml), whereas the iodoacetamide-inactivated A subuni t as well as the B subunit had no effect on permeability. Endothelial monol ayers exposed to the activated factor XIII A exhibited immunoreactive depos ition of itself at interfaces of adjacent cells; however, these were not fo und on exposure to nonactivated factor XIII A or factor XIII B. Hyperpermea bility induced by metabolic inhibition (1 mM potassium cyanide plus 1 mM 2- deoxy-D-glucose) was prevented in the presence of the activated factor XIII A. Likewise, the increase in myocardial water content in ischemic-reperfus ed rat hearts was prevented in its presence. This study shows that activate d factor XIII reduces endothelial permeability. It can prevent the loss of endothelial barrier function under conditions of energy depletion. Its effe ct seems related to a modification of the paracellular pas sageways in endo thelial monolayers.