title: Differential regulation of lung endothelial permeability in vitro and in situ.
abstract: In the lungs, increased vascular permeability can lead to acute lung injury. Because vascular permeability is regulated primarily by endothelial cells, many researchers have studied endothelial cell monolayers in culture, in order to understand the pathomechanisms of pulmonary edema. Such studies are based on the assumption that endothelial cells in culture behave like endothelial cells in situ. Here we show that this assumption is largely unfounded. Cultured endothelial cells show profound differences compared to their physiological counterparts, including a dysregulated calcium homeostasis. They fail to reproduce the pulmonary responses to agents such as platelet-activating factor. In contrast, they respond in a Rho-kinase depend fashion to thrombin, LPS or TNF. This is a striking finding for three reasons: (i) in the lungs, none of these agents increases vascular permeability by a direct interaction with endothelial cells; (ii) The endothelial Rho-kinase pathway seems to play little role in the development of pulmonary edema; (iii) This response pattern is similar for many endothelial cells in culture irrespective of their origin, which is in contrast to the stark heterogeneity of endothelial cells in situ. It appears that most endothelial in culture tend to develop a similar phenotyp that is not representative of any of the known endothelial cells of the lungs. We conclude that at present cultured endothelial cells are not useful to study the pathomechanisms of pulmonary edema.
authors: Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany.
authors: Stefan
authors: S
authors: Uhlig
authors: Yang
authors: Y
authors: Yang
authors: Josephine
authors: J
authors: Waade
authors: Claudia
authors: C
authors: Wittenberg
authors: Aaron
authors: A
authors: Babendreyer
authors: Wolfgang M
authors: WM
authors: Kuebler
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D011654:Pulmonary Edema / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D010972:Platelet Activating Factor; C060506:sphingosine 1-phosphate; D054460:rho-Associated Kinases; D013917:Thrombin; D013110:Sphingosine