The endoendothelial fibrin lining as the crucial barrier and the role of fibrin(ogenin) gels in controlling transcapillary transport

Abstract

The interface between the two portions of the ‘vessel-blood organ’, viz., the vessel wall and the circulating blood, is considered by the author to be the endoendothelial fibrin lining (EEFL). The view that the endothelium, consisting of the endothelial cells and the interendothelial cement substance, is the primary filtration barrier in capillary permeability (CP) is no longer tenable. There is considerable evidence that the primary barrier is an endocapillary protein layer, originally postulated by Danielli in 1940. Copley considered this layer to be identical with the EEFL formed in the more or less immobile portion of the plasmatic zone in close proximity to the vessel wall. Processes of fibrin formation and fibrinolysis can occur there homeostatically, undisturbed by the flow of blood. The fibrinopeptides and plasminopeptides, freed at this site by the conversion of fibrinogen to fibrin and of plasminogen to plasmin, respectively, were reported by Copley et al in 1966 to augment CP. These peptides thus take part in the steadily occurring normal physiological CP. This is facilitated by the porosity of the EEFL due to the network or gel structure of fibrin strands. The author’s concept that the EEFL acts as the primary barrier, controlling transendothelial transport and transport across the basement membrane (BM), is discussed on the basis of older and recent findings by several investigators. In particular, the BM is dealt with in some detail as a barrier. Emphasis is placed on the existence of fibrin as a main constituent of the BM, hitherto not generally known. This was demonstrated by direct evidence in the production of (non-thrombocytopenic) vascular purpura with fibrin antiserum. Numerous tiny foci of fibrin(ogenin) gels are expected to stud the BM. Augmented capillary fragility (CF) due to increased fibrinolysis of many of these focal fibrin gels result in petechial hemorrhages. CF and CP are physical properties of the blood capillary wall which behave antagonistically and are controlled by fibrin formation and fibrinolysis, steadily occurring in the vascular layers including the EM. This barrier secures the integrity of the capillary wall by preventing extravasation of blood or hemorrhages. New experimental approaches to verify the detection of fibrin in the microstructure of the capillary wall are proposed. Moreover, hemorheological experimentation, models and treatments are needed to establish whether or not the EEFL is the crucial, critical barrier in CP, as proposed.