It is this gap that allows accumulation of fluid, macromolecules, and white blood cells in the interstitium. Intracellular second messengers convey the message between circulating inflammatory mediators and the cell response, e.g. inter-cellular gaps. Cytosolic calcium and cyclic AMP are two important signals that control the endothelial cell barrier. Thus, increased calcium entry and decreased cyclic AMP promote inter-cellular gap formation during lung inflammation. Our ongoing studies aim to identify the calcium channel that is activated during inflammation to decrease cyclic AMP and promote inter-endothelial cell gap formation.
Inflammatory substances make endothelial cells pull apart, but the mechanism is unknown.
Endothelial cells tightly contact one another. Steven T, Nakahashi Y, Cornfield D, McMurtry I, Cooper D, and Rodman D. Calcium inhibitable adenylyl cyclase modulates pulmonary artery endothelial cell cAMP content and barrier function. Dempsey E, Stevens T, Durmowitz A, and Stenmark K. Mechanisms of hypoxia-induced change in contraction, growth, and matrix synthetic properties of pulmonary vascular cells. T. Stevens , B. Fouty, L. Hepler, D. Richardson, G. Brough, I.F. McMurtry, and D.M. Rodman. P.M. Chetham, W.D. Sefton, J. Bridges, T. Stevens , and I.F. McMurtry.