Distribution of type V secretory phospholipase A2 expression in human hepatocytes damaged by liver disease.
OBJECTIVE
Type V secretory phospholipase A2 (sPLA2-V) is a key enzyme in the arachidonate cascade. However, the distribution of sPLA2-V in human liver has not yet been investigated. In this study, the significance of sPLA2-V expression in human hepatocytes damaged by liver disease was investigated.


METHODS
Samples of liver tissue from patients with chronic hepatitis B and C, hepatitis virus-related liver cirrhosis, and congestive hepatocyte injury were immunostained with antibodies against sPLA2-V, cyclooxygenase (COX)-2, hepatitis viral antigens, transforming growth factor (TGF)-beta1, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha.


RESULTS
In chronic hepatitis patients, sPLA2-V-positive hepatocytes were scattered in the liver lobules, while cyclooxygenase-2, IL-1beta, and TNF-alpha were diffusely expressed. Hepatocytes around necroinflammatory lesions were strongly positive for sPLA2-V. Some sPLA2-V-positive hepatocytes were also positive for viral antigens. TGF-beta1 was expressed only in fibrotic lesions. The pattern of distribution of these proteins in liver cirrhosis patients was similar to that in chronic hepatitis patients, but sPLA2-V expression tended to be more intense than in chronic hepatitis. In the congestive liver, sPLA2-V, COX-2, and the two cytokines were diffusely expressed in surviving hepatocytes.


CONCLUSIONS
sPLA2-V expression in hepatocytes is induced by viral infection, fibrosis, and circulatory disturbance. Immunostaining using sPLA2-V antibody is useful for the detection of injured hepatocytes in patients with liver diseases.
Ito
Masamichi
M
Department of Pathology, Toho University School of Medicine, Tokyo, Japan. happy@med.toho-u.ac.jp
Ishikawa
Yukio
Y
Kiguchi
Hideko
H
Komiyama
Kazuo
K
Murakami
Makoto
M
Kudo
Ichiro
I
Akasaka
Yoshikiyo
Y
Ishii
Toshiharu
T
D000328:Adult; D000368:Aged; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D054505:Group V Phospholipases A2; D018963:Hepatitis Antigens / Q000096:biosynthesis; D006525:Hepatitis, Viral, Human / Q000473:pathology / Q000503:physiopathology; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010741:Phospholipases A / Q000096:biosynthesis*; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis
D016207:Cytokines; D018963:Hepatitis Antigens; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054505:Group V Phospholipases A2; D054467:Phospholipases A2; C101424:phospholipase A2-V, Trimeresurus