Regulation of endothelial barrier responses and permeability

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

The endothelial cell (EC) lining of the systemic and pulmonary vasculatures was considered for decades to exist merely as an inert and passive semipermeable cellular barrier between the blood and the interstitium of all tissues. During the early 1960s, however, Majno and Palade described the ultrastructural appearance of an actively contracted endothelium in pulmonary vessels previously exposed to the edemagenic agent histamine (1), thus igniting a controversy over whether the endothelium plays an active role in the inflammatory response. It is now well recognized that endothelial activities are critical and essential aspects of inflammation. Disruption of the integrity of the endothelial barrier results in marked increases in permeability to fluids leading to tissue edema and pain (dolor), and leukocyte infiltration into tissues (rubor and calor). When persistent and of significant intensity, this process invariably progresses to organ dysfunction. For example, in systemic inflammatory states such as sepsis, increased vascular permeability results in high morbidity and mortality via multiorgan dysfunction, including acute renal or hepatic failure, cardiac dysfunction, and respiratory insufficiency. Despite multiple attempts to improve upon the adverse clinical outcomes associated with increased endothelial permeability, the termination of fulminant edema with restoration of endothelial integrity remains an unrealized goal. Considerable progress in the past several years, however, suggests that several barrier-enhancing agents (or their selective derivatives with greater receptor selectivity) may be on the horizon for therapeutic purposes. It also should be noted that in selective vascular cells such as the cerebral circulation, the goal may be to actually increase permeability in order to increase the access of novel therapeutics across the blood–brain barrier (Figure 113.1).

Original languageEnglish (US)
Title of host publicationEndothelial Biomedicine
PublisherCambridge University Press
Pages1015-1029
Number of pages15
ISBN (Electronic)9780511546198
ISBN (Print)0521853761, 9780521853767
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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