SIGNAL-TRANSDUCTION AND REGULATION OF LUNG ENDOTHELIAL-CELL PERMEABILITY - INTERACTION BETWEEN CALCIUM AND CAMP

1998.--Pulmonary endothelium forms a semiselective barrier that regula tes 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 prot einaceous fluid from blood into the interstitium. Intracellular signal s activated by neurohumoral mediators and oxidants that evoke intercel lular gap formation are incompletely understood. Cytosolic Ca2+ concen tration ([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 enhance s endothelial barrier function. Furthermore, during the course of infl ammation, elevated endothelial cell [Ca2+](i) decreases cAMP to facili tate 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 signali ng pathways. Emerging data also indicate that endothelial cells derive d from different vascular sites within the pulmonary circulation exhib it distinct sensitivities to permeability-inducing stimuli; that is, e levated [Ca2+](i) promotes macrovascular but not microvascular barrier disruption. Thus this review also considers the roles of [Ca2+](i) an d cAMP in mediating site-specific alterations in endothelial permeabil ity.