Neutrophil-mediated tissue injury in alcoholic hepatitis.
The presence of polymorphonuclear leukocytes (neutrophils) in liver parenchyma is a prominent feature of alcoholic hepatitis. However, the pathophysiological importance of these phagocytes and potential injury mechanisms in alcoholic hepatitis remain unclear. This review summarizes the current knowledge on basic mechanisms of neutrophil-induced liver injury as it emerged from studying a number of different experimental models. This general concept of neutrophil-mediated liver cell injury agrees with many observations made by examining liver sections obtained from patients with alcoholic hepatitis. These include the presence of extravasated neutrophils in the liver, evidence for degranulation of neutrophils in the parenchyma, and excessive formation of neutrophil chemoattractants such as CXC chemokines in liver cells. Colocalization and a strong quantitative correlation between apoptotic hepatocytes and neutrophils could indicate apoptosis-induced transmigration of neutrophils during alcoholic hepatitis, similar to events previously demonstrated in experimental models. Furthermore, circulating neutrophils are primed for reactive oxygen species and inflammatory mediator formation. However, clear evidence for a neutrophil-induced injury in alcoholic hepatitis is missing. Unfortunately, most experimental models of alcoholic liver disease do not have a prominent neutrophilic infiltrate. Therefore, a high priority of future research has to be to develop an experimental model that realistically mimics the neutrophil component of alcoholic hepatitis in human beings. This would allow investigators to test the concept that neutrophils are important for cell injury during alcoholic hepatitis and to identify potential therapeutic intervention strategies.
Jaeschke
Hartmut
H
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Mailslot 638, Little Rock, AR 72205-7199, USA. JaeschkeHarmutW@uams.edu
D000818:Animals; D004195:Disease Models, Animal; D006519:Hepatitis, Alcoholic / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*