Tm. Moore et al., SIGNAL-TRANSDUCTION AND REGULATION OF LUNG ENDOTHELIAL-CELL PERMEABILITY - INTERACTION BETWEEN CALCIUM AND CAMP, American journal of physiology. Lung cellular and molecular physiology, 19(2), 1998, pp. 203-222
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.