Control of vascular endothelial cell barrier function results from a delicate balance between contractile and tethering forces that is significantly regulated by cross-linking of MT and actin cytoskeletal networks. Disruption of the MT network appears to set off a cascade of downstream effects on Rho-dependent mechanisms, including release of MT-bound GEFs and subsequent activation of the small GTPase Rho and Rho kinase, which ultimately results in a significant increase in MLC phosphorylation and subsequent contractile force.
Multiple factors regulate the actomyosin and MT-dependent effect on EC permeability. These include the barrier-protective effect of the cAMP-dependent protein kinase A (PKA) which likely stabilizes the MT network and retards Rho kinase activation by RhoGEFs .
Inflammatory cytokines such as tumor necrosis factor (TNF)-a that are secreted by macrophages and endothelial cells increase EC permeability. Presence of TNF-a also induces destabilization of microtubules. TNF-a induces MLC phosphorylation accompanied by microfilament rearrangement; however, subsequent EC permeability appears to be independent of MLCK and Rho kinase. Microtubule disassembly most likely affects TNF-a induced actin network changes and EC permeability.
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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.