Cell biology of pulmonary endothelium

Since the late 1960s, understanding of the cell biology of endothelium has been transformed. Endothelium is not merely a metabolically inert, semipermeable barrier separating blood from parenchyma; rather, it is a layer of metabolically active cells. In lungs, even gas exchange may be assisted by reactions occurring on the endothelial surface. Endothelial cells synthesize specific proteins (some for export); these cells have receptors and enzymes capable of reacting with certain hormones and other excitatory substances as they pass in circulating blood. Endothelium is antithrombogenic unless injured; when injured, endothelium becomes thrombogenic and then thrombolytic. Endothelium may sometimes retard the development of inflammation and at other times may facilitate it. In addition to providing sites for exchange of nutrients and metabolites, endothelium interacts with prohormones and hormones to determine the composition of blood moving downstream. The latter is a key function of pulmonary endothelium: its venous effluent is systemic arterial blood. Efforts to understand how endothelium accomplishes its wide range of metabolic activities have motivated parallel efforts to define the fine structure of the endothelial cell. Thus it has become feasible to visualize habitats of two surface enzymes, angiotensin-converting enzyme and carboxypeptidase N. Efforts to visualize surface enzymes required development of means of replicating cell surfaces, a methodology that in turn provided the first en face view of the glycocalyx. Given the ubiquity of vascular endothelium and its activities, it is difficult to imagine an area of medical practice that can safely ignore requirements for appropriately functioning endothelium.