New developments in lung endothelial heterogeneity: Von Willebrand factor, P-selectin, and the Weibel-Palade body

Abstract

Quiescent pulmonary endothelium establishes an antithrombotic, anti-inflammatory surface that promotes blood flow. However, the endothelium rapidly responds to injury and inflammation by promoting thrombosis and enabling the directed transmigration of inflammatory cells, such as neutrophils, into the alveolar airspace. Although the endothelial cell signals responsible for establishing a prothrombotic surface are distinct from those responsible for recognizing circulating neutrophils, these processes are highly interrelated. Von Willebrand factor (VWF)-stimulated secretion plays an important role in thrombus formation, and P-selectin surface expression plays a key role in neutrophil binding necessary for transmigration. Both VWF and P-selectin are located within Weibel-Palade bodies in pulmonary arteries and arterioles, yet Weibel-Palade bodies are absent in capillaries. Despite the absence of the Weibel-Palade bodies, pulmonary capillaries express both VWF and P-selectin. The physiological and pathophysiological significance of these observations is unclear. In this review, we address some anatomical and physiological features that distinguish pulmonary artery, capillary, and vein endothelium. In addition, we review our current understanding regarding the stimulated secretion of VWF and P-selectin in pulmonary artery and capillary endothelium. This information is considered in the context of vasculitis and pneumonia, two pathophysiological processes to which the stimulated secretion of VWF and P-selectin contribute.

Figure 1

Scanning electron micrograph of a methylmethacrylate casted lung reveals both the pulmonary macro- and microcirculation. A. Arrow points to extra-alveolar vessel. Scale 100 μm. B. Pulmonary microcirculation. White arrowheads point to arterioles and capillaries. Scale 50 μm. Electron micrographs courtesy of Dr. Diego Alvarez.

Figure 2

Transmission electron micrographs of rat lung endothelium. A. Pulmonary artery endothelial cells. B. Pulmonary capillary endothelial cells. Scale 2 μm. Micrographs courtesy of Dr. Judy A. King.

Figure 3

Flow cytometry analysis of lung endothelium. Pulmonary artery endothelial cells bind to PECAM-1, VE-cadherin, von Wilebrand factor and Helix pomatia. Pulmonary capillary endothelial cells bind to PECAM-1, VE-cadherin, von Wilebrand factor and Griffonia simplicifolia. Adapted from , with permission.

Figure 4

Transmission electron micrographs of human lung endothelium. A. Pulmonary artery endothelial cells contain Weibel-Palade bodies (black arrowheads). B. Pulmonary capillary endothelial do not contain Weibel-Palade bodies; however, they contain large number of caveolea. Scale 200 nm. Micrographs courtesy of Dr. Judy A. King.