The pulmonary microvessels serve as primary sites for fluid and solute exchange within the lung tissue. Starling forces govern fluid filtration from microvessels into the surrounding perimicrovascular interstitial space. The pulmonary lymphatics collect fluid and protein leaking into the interstitium and return the fluid and dissolved solute to the vascular system. Pathophysiologic events and mediators that substantially perturb the Starling forces culminate in pulmonary edema.
Adherens junction: An anchoring junction between two cells (made up of cadherin and associated proteins) that is linked to the actin cytoskeleton.
Edema: Swelling or excessive buildup of fluid in the tissues, or an increase in tissue mass due to fluid accumulation.
Fluid filtration: The passage of a liquid through a porous membrane resulting from a hydrostatic pressure difference.
Reflection coefficient: A measure of the relative permeability of a particular membrane to a particular solute calculated as the ratio of observed osmotic pressure to that calculated from van't Hoff's law.
Vascular permeability: The velocity of transport through the endothelial barrier through any or all of the following pathways: (1) between the cells, (2) through the cells, via pores (diaphragms or fused vesicles), and (3) transcellularly, via shuttling vesicles and specific receptors.
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Minshall, R. D., Tiruppathi, C., Vogel, S. M., and Malik, A. B. (2002). Vesicle formation and trafficking and its role in regulation of endothelial barrier function. Histochem. Cell Biol. 117, 105-112. This review outlines the signaling mechanisms involved in caveolae-mediated endocy-tosis and transcytosis of albumin in endothelial cells. This transcellular transport mechanism is an important determinant of basal albumin permeability and nutrient/hormone delivery into the tissue when cell—cell junctions are intact.
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Tuma, P. L., and Hubbard, A. L. (2003). Transcytosis: Crossing cellular barriers. Physiol. Rev. 83, 871-932. Tiruppathi, C., Minshall, R. D., Paria, B. C., Vogel, S. M., and Malik, A. B. (2003) Role of Ca2+ signaling in the regulation of endothelial permeability. Vasc. Pharmacol. 39, 173-185. This review summarizes the mechanisms which regulate intracellular calcium homeostasis (release mechanisms and influx pathways) in endothelial cells and their role in thrombin-induced increase in endothelial permeability.
Dr. Richard Minshall is an Assistant Professor of Pharmacology and Anesthesiology at The University of Illinois at Chicago. A Parker Francis Fellow in Pulmonary Research from 2001 to 2004, his NIH-funded research focuses on the physiological and pathological roles transcellular and paracellular permeability pathways of the endothelium.
Dr. Stephen Vogel is an Assistant Professor of Pharmacology at The University of Illinois at Chicago investigating the mechanisms of protein and fluid permeability regulation in the lung. Dr. Vogel is regarded as a significant contributor in the lung biology field for the development of ex vivo isolated mouse and rat lung models used to investigate the physiological importance of caveolae-mediated albumin transport processes in the epithelial and endothelial cell barriers.
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