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Integrated Control of Lung Fluid Balance
APS Respiration Section
Dolly Mehta and Asrar B. Malik
A.B. Malik, J. Bhattacharya, D. Mehta and M.A. Matthay
The pathophysiologic mechanisms leading to pulmonary edema such as
“high-permeability” type of pulmonary edema and alveolar fluid accumulation
remain unclear. The basis of resolution of tissue edema also remains poorly
understood. Given the vast surface area of pulmonary microcirculation and
its close association with gas-exchanging alveolar epithelial barrier,
integrity of both microvessel and alveolar epithelial barriers will
determine lung fluid balance. Disruption of either barrier results in
leakage of fluid and macromolecules into the interstitium and alveolar
space. This condition is clinically manifested as high permeability,
protein-rich pulmonary edema. Although many recent studies have emphasized
mechanisms of endothelial and epithelial alterations at the cellular level
often using cell culture systems, the integrated picture of how barriers are
disrupted and how tissue fluid can be resolved needs to be highlighted.
Hence, the purpose of this symposium. In this symposium, the four talks
will address at the integrated systems level the control of fluid
homeostasis and the signaling mechanisms involved. The emphasis will be on
recent studies made in the intact lung so as to provide a picture of
integrated aspects of lung fluid balance. These topics will include:
mechanosensitive-regulation of lung fluid balance, role of Rho activation in
regulating pulmonary vascular permeability, role of adherens junction in
vivo, and mechanisms of active fluid clearance from lung. Dr. Jahar
Bhattacharya will address the role of lung capillary pressure in the
generation of pro-inflammatory response. He will also describe how Ca2+
signaling, expression of adhesive proteins and cell-cell junction proteins
as induced by pressure elevation regulate lung-fluid balance. Dr. Dolly
Mehta will describe her recent findings addressing the role of Rho-induced
cytoskeletal changes in regulating endothelial barrier function in vivo.
Since active ion transport is the primary mechanism responsible for the
removal of fluid from distal air spaces of lung, Dr. Michael Matthay, will
outline the role of cAMP signaling regulating the rate of alveolar fluid
clearance, including the role of hormonal factors, cytokines, and growth
factors. 4) Dr. A. B. Malik will address the role of adherens junctions in
the regulation of pulmonary microvessel permeability in vivo.
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