Tumor necrosis factor-a (TNF-a) is a major proinflammatory cytokine secreted in increased amounts by macrophages and endothelial cells in situations linked pulmonary edema formation, such as pneumonia, sepsis, systemic inflammation and injury. TNF-a has been implicated in endothelial cell activation, endothelial cell death by apop-tosis, and increased vascular permeability. The mechanisms by which TNF-a triggers endothelial barrier disruption include contraction of the intracellular actin microfilaments and formation of inter-cellular gaps that parallel in time the development of trans-endothelial permeability . The rearrangement of the actin-based cytoskeleton is the result of actin-myosin movement, which, as in muscle cells, follows the phosphorylation of the myosin light chains. TNF-a induces significant actin microfilaments contraction via myosin light chain phosphorylation, a reaction catalyzed by both myosin light chain kinase (MLCK) and Rho kinase. However, inhibition of either enzyme does not prevent TNF-a-induced endothelial barrier dysfunction , suggesting that MLCK-independent microfilament changes and/or other cytoskeletal structures, such as intermediate filaments, microtubules, and adherens junctions, may be involved.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.