Edward Weibel and George Palade made a remarkable discovery in 1964. Surveying human lungs with an electron microscope, they saw a “hitherto unknown rod-shaped cytoplasmic component … in endothelial cells of small arteries” (1). These rods, measuring 0.1 μm thick and 3 μm in length, contained dense material organized as fibers running parallel to the long axis (Figure 72.1; for color reproduction, see Color Plate 72.1A). Weibel and Palade concluded that the “nature and significance of these cytoplasmic components are yet unknown.”

Over the last four decades, we have learned an enormous amount about these endothelial-specific organelles, now called Weibel-Palade bodies (WPBs). WPBs are regulated secretory granules. Within seconds of vascular injury, endothelial cells (ECs) activate the internal exocytic machinery, driving fusion of the WPBs with the cellular membrane. WPBs contain a variety of compounds that, once released into the blood, activate vascular inflammation and thrombosis (Figure 72.2). WPB exocytosis is the initial response of the vasculature to injury.

However, a number of intriguing questions about WPBs remain unanswered. Why are specific proteins targeted to enter the WPBs, whereas other cargo is excluded? How are WPBs directed to fuse with the plasma membrane and not with other organelles? Which vascular beds contain the most endothelial granules, and why? Finally, are endothelial granules capable of plasticity? Do the contents of these WPBs change as their environment changes, giving the ECs the ability to alter their response as their own environment changes, thus reflecting a vascular memory?

CONTENTS OF WEIBEL-PALADE BODIES

WPBs contain molecules that regulate thrombosis and inflammation, as well as other vascular regulators (Table 72.1). The predominant component of WPB is von Willebrand factor (vWF) (2).