Understanding the mechanisms of lung mechanical stress

Abstract

Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area) or strain (any forced change in length in relation to the initial length) and shear stress (the stress component parallel to a given surface). The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical forcerelated disorders.

How Do Dual Long-Acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?

“…Hyperinflation may also result in alveolar stress and release of inflammatory cytokines. This potential inflammatory effect might also be reduced by administration of effective long-acting bronchodilation (58). The improvement in lung mechanics, combined with the reduction in dyspnea and the potential reduction of mechanical …”

Lamellar Body Exocytosis by Cell Stretch or Purinergic Stimulation: Possible Physiological Roles, Messengers and Mechanisms

“…(ECM)/integrin signalling, gene expression, cytokine release and type II cell function/phenotype has been reviewed in detail elsewhere [22,27,[54][55][56][57]. Hindering integrin interaction with the ECM by RGD (Arg-Gly-Asp) peptides inhibits the stretch-induced Ca 2+ signal (G. Fois, unpublished observation).…”

Stimulation of Rho signaling by pathologic mechanical stretch is a “second hit” to Rho-independent lung injury induced by IL-6

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“…Pathologic mechanical forces leading to VILI trigger several signaling mechanisms including activation of signaling kinases, ion channels, small GTPases, second messengers, inflammatory signaling, and gene expression (14,16,39). Increased vascular endothelial permeability (2), inflammatory cytokine production (41), and apoptosis (18) induced by pathological mechanical stimulation causes alveolar flooding, leukocyte infiltration, and hypoxemia leading to morbidity and mortality (26,34).…”