Free radicals, chemokines, and cell injury in HIV-1 and SIV infections and alcoholic hepatitis.
Oxidative stress has been observed in HIV-1 infection and alcoholic liver disease. The formation of reactive oxygen species (ROS) contributes to cell injury through apoptosis and/or necrosis and secretion of proinflammatory cytokines and chemokines. The major sources of ROS and chemokines are the Kupffer cells. During chronic ethanol consumption they are primed and activated for enhanced formation of pro-inflammatory factors, probably as a result of ethanol-induced translocation of gut-derived endotoxin into the circulation. Pro-inflammatory factors produced in the liver stimulate neutrophilic and/or lymphocytic infiltration to this organ. The presence of inflammatory cells in the liver may compromise the hepatocytes to injury by releasing cytotoxic factors, i.e., ROS, cytolytic proteases. Kupffer cells also interact with the glycoprotein 120 of SIV and HIV-1, which can induce oxidative stress and chemokine release. CD4+ lymphocytes that are infected with the virus generate intracellular ROS, which in turn leads to apoptosis and cell death. Downregulation of CD4+ cells contributes to immunodeficiency, while enhanced sequestration of inflammatory cells in the liver during chronic ethanol use with or without HIV-1/SIV may result in hepatocyte injury and exacerbation of alcoholic liver disease.
Bautista
A P
AP
Department of Physiology and NIAAA-Sponsored Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. abauti@lsuhsc.edu
D000438:Alcohols / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018925:Chemokines / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology*; D006519:Hepatitis, Alcoholic / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008253:Macaca mulatta; D009336:Necrosis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism / Q000473:pathology*
D000438:Alcohols; D018925:Chemokines; D005609:Free Radicals