The barrier function of the endothelium is impaired in inflammatory states with the accumulation of protein rich fluid in the interstitium. Changes in permeability in the endothelium are linked to leucocyte adhesion as outlined above.
The three ways by which solutes reach the interstitium are diffusion, vesicular transport and between the endothelial cells. Small solutes pass through the endothelium by simple diffusion. Larger solutes are taken up by the endothelial cell in vesicles which are transported across the cell. There are specialized junctions between the endothelial cells which are altered to allow leucocytes and large solutes through. Stimulation by pro inflammatory mediators such as histamine and thrombin results in retraction and separation of endothelial cells for a period. The result is the accumulation of protein rich fluid in the interstitium and oedema. Separation of the endothelial cells is reversible over a few minutes.
In ischemia reperfusion injury there is a temporal relationship between the migration of leucocytes and the transfer of albumin. The more leucocytes adhering and migrating the greater the amount of albumin transfer and monoclonal antibodies that attenuate leucocyte adhesion and migration also reduce albumin leakage.
The vascular leak syndrome, which occurs clinically in patients administered large doses of IL-2 is due to increased endothelial premeability.