title: Increased activity of the complement system in the liver of patients with alcoholic hepatitis.
abstract: Inflammation has been suggested as a mechanism underlying the development of alcoholic hepatitis (AH). The activation of the complement system plays an important role in inflammation. Although it has been shown that ethanol-induced activation of the complement system contributes to the pathophysiology of ethanol-induced liver injury in mice, whether ethanol consumption activates the complement system in the human liver has not been investigated. Using antibodies against C1q, C3, and C5, the immunoreactivity of the complement system in patients with AH was examined by immunohistochemistry and quantified by morphometric image analysis. The immunoreactivity intensity of C1q, C3, and C5 in patients with AH was significantly higher than that seen in normal controls. Further, the gene expression of C1q, C3, and C5 was examined using real-time PCR. There were increases in the levels of C1q and C5, but not C3 mRNA in AH. Moreover, the immunoreactivity of C5a receptor (C5aR) also increased in AH. To explore the functional implication of the activation of the complement system in AH, we examined the colocalization of C5aR in Mallory-Denk bodies (MDBs) forming balloon hepatocytes. C5aR was focally overexpressed in the MDB forming cells. Collectively, our study suggests that alcohol consumption increases the activity of the complement system in the liver cells, which contributes to the inflammation-associated pathogenesis of AH.
authors.affiliation: Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA 90509, USA. Electronic address: hongshenmail@gmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.affiliation: LA BioMed at Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: French
authors.affiliation: LA BioMed at Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: LA BioMed at Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
authors.forename: Brittany C
authors.initials: BC
authors.lastname: Tillman
authors.affiliation: LA BioMed at Harbor-UCLA Medical Center, Torrance, CA 90509, USA; Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
mesh_terms: D003167:Complement Activation / Q000187:drug effects*; D003165:Complement System Proteins / Q000187:drug effects*; D000431:Ethanol / Q000009:adverse effects; D006519:Hepatitis, Alcoholic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D059609:Mallory Bodies / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000431:Ethanol; D003165:Complement System Proteins
keywords: Alcoholic hepatitis; Complement factors; Inflammation; Mallory–Denk bodies