Aster V7 Activation 154

Immune surveillance and activation may be controlled by a wide variety of extrinsic cues. Control points for acute inflammatory responses such as bacterial infections and injury are found in the liver. The liver is protected from microbial challenge due to the sequestration of potential pathogens (including bacteria, viruses, fungal elements, and prions) in the portal circulation. This is accomplished by hepatic sinusoids that contain high endothelial venules and a thin layer of albumin-filled capillaries that restrict direct interactions between circulating pathogens and endothelial cells that constitute the walls of the liver sinusoids. However, microbes and other foreign particles can enter the liver via intercellular spaces in the portal venous circulation and via the lymphatics, the biliary tract, and other sites. The liver produces an array of antimicrobial substances including NOS inhibitors, anti-bacterial peptides, proteases, vitamins A, D, and K, and the most abundant complement proteins ( CH1, CH2, and C3 (but not C4)); this system acts synergistically to promote bacterial clearance.

aster v7 activation 154

Cholestatic liver disease can result in activation of HSC due to a primary defect in hepatocyte bile acid (BA) synthesis or due to endothelial cell injury that causes chronic liver injury leading to fibrosis. Under physiologic conditions, biliary BA secretion by hepatocytes into the bile canaliculi is brought to a halt by decreased expression of the apical bile acid export pump, BSEP. Cholestasis can be caused by several insults that include bile acid toxicity, obstruction, bacterial overgrowth, alcohol consumption, metabolic factors, or genetic factors. Bile acids are essential for efficient digestion of lipid-rich meals. Bile acids are synthesized from cholesterol in the liver; they are then delivered to the gallbladder and released into bile where they aid in the digestion of dietary lipids. There are several species of bile acids, including cholesterol, and they each play specific physiological roles in lipid digestion. Other members of the steroid hormone class are also synthesized in the liver.