Signal transduction and regulation of lung endothelial cell permeability. Interaction between calcium and cAMP.
Pulmonary endothelium forms a semiselective barrier that regulates fluid balance and leukocyte trafficking. During the course of lung inflammation, neurohumoral mediators and oxidants act on endothelial cells to induce intercellular gaps permissive for transudation of proteinaceous fluid from blood into the interstitium. Intracellular signals activated by neurohumoral mediators and oxidants that evoke intercellular gap formation are incompletely understood. Cytosolic Ca2+ concentration ([Ca2+]i) and cAMP are two signals that importantly dictate cell-cell apposition. Although increased [Ca2+]i promotes disruption of the macrovascular endothelial cell barrier, increased cAMP enhances endothelial barrier function. Furthermore, during the course of inflammation, elevated endothelial cell [Ca2+]i decreases cAMP to facilitate intercellular gap formation. Given the significance of both [Ca2+]i and cAMP in mediating cell-cell apposition, this review addresses potential sites of cross talk between these two intracellular signaling pathways. Emerging data also indicate that endothelial cells derived from different vascular sites within the pulmonary circulation exhibit distinct sensitivities to permeability-inducing stimuli; that is, elevated [Ca2+]i promotes macrovascular but not microvascular barrier disruption. Thus this review also considers the roles of [Ca2+]i and cAMP in mediating site-specific alterations in endothelial permeability.
Department of Pharmacology and Lung Biology and Pathology Research Laboratory, University of South Alabama College of Medicine, Mobile, Alabama 36688, USA.
T M
TM
Moore
P M
PM
Chetham
J J
JJ
Kelly
T
T
Stevens
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability; D000242:Cyclic AMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007249:Inflammation; D007962:Leukocytes / Q000502:physiology; D011652:Pulmonary Circulation; D015398:Signal Transduction; D014882:Water-Electrolyte Balance
D000242:Cyclic AMP; D002118:Calcium