Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1018-1023
© 1997 American Heart Association, Inc.
Articles |
Endothelial Permeability for Macromolecules
Mechanistic Aspects of Pathophysiological Modulation
From the Gaubius Laboratory TNO-PG, Leiden, and the Institute for Cardiovascular Research, Free University, Amsterdam, the Netherlands.
Correspondence to Prof V. van Hinsbergh, Gaubius Laboratory TNO-PG, Zernikedreef 9, PO Box 2215, 2301 CE Leiden, Netherlands.
Key Words: endothelium • permeability • phosphorylation
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Introduction |
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The endothelium separates blood from tissue and actively regulates the exchange between these compartments. Throughout the body, this one-cell-thick lining of blood vessels extends over several thousand square meters. It harbors many receptors and functions that actively regulate the extravasation of nutrients, solutes, hormones, macromolecules, and leukocytes. If the barrier function of the endothelium does not perform appropriately, leakage of macromolecules occurs, causing edema formation and exposure of the interstitium to high concentrations of plasma constituents. In severe cases of vascular leakage, platelets will adhere to the exposed subendothelium and red blood cells may even accumulate in the interstitium. Vascular leakage may be desirable for recruiting plasma proteins, such as complement factors during infection, but it can become life-threatening, particularly when it occurs in the lungs or pericardium or when it causes hypovolemic shock. Furthermore, frequent or prolonged leakage may impair proper functioning of the affected tissue. In recent years, considerable progress has been made in understanding the molecular processes that contribute to the regulation of endothelial permeability.
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Nature of the Endothelial Barrier |
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With the exception of the liver, adrenal, and bone marrow sinusoids, in which the endothelium has rather large pores, the endothelium constitutes a selective barrier between blood and tissue. In principle, this barrier consists of the EC monolayer and its matrix. Macromolecules can cross the endothelial barrier in three ways: (1) between the cells, through cell junctions (paracellular); (2) through the EC, via pores (diaphragms or fused vesicles); and (3) transcellularly, via shuttling vesicles and specific receptors. It is generally believed that
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