Abstract Pain, redness, heat, and swelling are hallmarks of inflammation that were recognized as early as the first century AD. Despite these early observations, the mechanisms responsible for swelling, in particular, remained an enigma for nearly two millennia. Only in the past century have scientists and physicians gained an appreciation for the role that vascular endothelium plays in controlling the exudation that is responsible for swelling. One of these mechanisms is the formation of transient gaps between adjacent endothelial cell borders. Inflammatory mediators act on endothelium to reorganize the cytoskeleton, decrease the strength of proteins that connect cells together, and induce transient gaps between endothelial cells. These gaps form a paracellular route responsible for exudation. The discovery that interendothelial cell gaps are causally linked to exudation began in the 1960s and was accompanied by significant controversy. Today, the role of gap formation in tissue edema is accepted by many, and significant scientific effort is dedicated toward developing therapeutic strategies that will prevent or reverse the endothelial cell gaps that are present during the course of inflammatory illness. Given the importance of this field in endothelial cell biology and inflammatory disease, this focused review catalogs key historical advances that contributed to our modern-day understanding of the cell biology of interendothelial gap formation. inflammation permeability transport junctions endothelium Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print September 2011 , doi: 10.​1152/​ajplung.​00215.​2011 AJP - Lung Physiol February 2012 vol. 302 no. 3 L275-L286 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajplung.00215.2011v1 302/3/L275 most recent Classifications Review Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Ochoa, C. D. Articles by Stevens, T. PubMed PubMed citation Articles by Ochoa, C. D. Articles by Stevens, T. Related Content Load related web page information Current Issue February 2012, 302 (3) Alert me to new issues of AJP - Lung Physiol About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 1040-0605 Online ISSN: 1522-1504 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

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