The application of electron microscopy to biological research initially required intensive investigation directed toward improvements in instrumentation and specimen preparation. As these investigations progressed, ultrastructural descriptions of the cell, different cells, and subcellular organelles common to cells and those which are distinctive of specific cell lineages emerged. Application of ultrastructural studies to the endothelium facilitated understanding of endothelial cell (EC) biology. In this chapter, we review the contributions of electron microscopy to this understanding, which was established during the 1950s and 1960s.

CONTRIBUTIONS ESTABLISHED DURING 1950–1959

The endothelium provides a physical barrier between the vascular lumen and the extravascular tissue space. All blood vessels are lined by interconnected ECs that comprise the endothelial layer. Before the electron microscope was developed, knowledge of EC structure and function was based primarily on physiological and light microscopic studies. One of the primary uses of the electron microscope was to confirm or deny the prevalent theories and findings obtained with these methods. Thus, by the late 1940s, physiologists had modeled the necessity for pores of small and large sizes in the endothelium to explain permeability data (1), and light microscopic studies proposed an intercellular cement to account for the connection between adjacent ECs (2). As well as re-examining such issues with the electron microscope, studies proceeded on the anatomic organization, heterogeneity of different vascular beds, classification of types of microvessels, and description of individual cellular components of small vessels and of the organelle content of microvascular endothelium (3). Early studies using tracers to probe permeability possibilities began during the 1950s, as well as studies of the mediator-induced leaking vessels characteristic of inflammatory changes involving small vessels (4).