User:Marvin O'Neal/OspA: Difference between revisions
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<h3>Evasion and the Extracellular Matrix</h3> | <h3>Evasion and the Extracellular Matrix</h3> | ||
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The <i>Borrelia</i> are able to hide in the [http://en.wikipedia.org/wiki/Extracellular_matrix extracellular matrix], allowing it to survive by avoiding [http://en.wikipedia.org/wiki/Leukocytes leukocytes] circulating in the bloodstream. OspA can rapidly bind to plasminogen, which becomes [http://en.wikipedia.org/wiki/Plasmin plasmin] once activated, and degrades the extracellular matrix. By binding to plasminogen, <i>Borrelia</i> could be exploiting its function and utilizing it to invade the extracellular matrix. However, due to the fact that OspA is downregulated during feeding, and stays unexpressed, a different mechanism may be used instead. Additionally, <i>Borrelia</i> induces the local upregulation of matrix metalloproteinase-9, causing the digestion of the surrounding extracellular matrix. <i>Borrelia</i> can also bind to several proteins in the extracellular matrix, such as [http://en.wikipedia.org/wiki/Fibronectin fibronectin], [http://en.wikipedia.org/wiki/Integrins integrins] or [http://en.wikipedia.org/wiki/Decorin decorin], which can aid in the spread and survival of the spirochetes in these tissues. | The <i>Borrelia</i> are able to hide in the [http://en.wikipedia.org/wiki/Extracellular_matrix extracellular matrix], allowing it to survive by avoiding [http://en.wikipedia.org/wiki/Leukocytes leukocytes] circulating in the bloodstream. OspA can rapidly bind to plasminogen, which becomes [http://en.wikipedia.org/wiki/Plasmin plasmin] once activated, and degrades the extracellular matrix. By binding to plasminogen, <i>Borrelia</i> could be exploiting its function and utilizing it to invade the extracellular matrix. However, due to the fact that OspA is downregulated during feeding, and stays unexpressed, a different mechanism may be used instead. Additionally, <i>Borrelia</i> induces the local upregulation of matrix metalloproteinase-9, causing the digestion of the surrounding extracellular matrix. <i>Borrelia</i> can also bind to several proteins in the extracellular matrix, such as [http://en.wikipedia.org/wiki/Fibronectin fibronectin], [http://en.wikipedia.org/wiki/Integrins integrins] or [http://en.wikipedia.org/wiki/Decorin decorin], which can aid in the spread and survival of the spirochetes in these tissues.<ref name="rupprecht">PMID: 18097481</ref> | ||
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<h3>Migration Across the Blood-Brain Barrier</h3> | |||
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It is not fully understood how <i>Borrelia</i> get past the [http://en.wikipedia.org/wiki/Blood-brain_barrier blood-brain barrier], though some researchers suggest a paracellular route, which involves a process using transient tether-type associations, short-term dragging interactions, and stationary adhesion. There is evidence that <i>Borrelia</i> utilizes OspA in the transient tethering stage. The blood-brain barrier is composed of brain microvascular endothelial cells, astrocytes, a basement membrane, pericytes, and neurons. OspA is a major adherent molecule to brain microvascular cells by binding to the CD40 receptors outside, which results in events that are typically seen when leukocytes cross the blood brain barrier. | |||
Activation of CD40 receptors leads to the production of proinflammatory cytokines and enhanced expression of ICAM-1, E-selectin and VCAM-1, resulting in increased cell binding, and the formation of fenestrations due to increased vascular endothelial growth factor, and vascular permeability factor. OspA might be mimicking leukocytes in order to cross the blood brain barrier. However not all strains of borrelia can utilize OspA to do this, OspA only contributes about 70% to adherence, and other <i>Borrelia</i> proteins are also needed in this process. It has also been seen that OspA mediates the adhesion of <i>Borrelia</i> to murine neural and glial cell lines. <ref name="pulzova">PMID: 22355605</ref> | |||
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