Expression of the beta 1 chain (CD29) of integrins and CD45 in alcoholic liver disease. The VA Cooperative Study Group No. 275.
OBJECTIVE
In the active stages of alcoholic liver disease (ALD), we have shown previously an enhanced expression of either CD4 or CD8 molecules on CD3+T cells. Class I and II MHC molecules expression were enhanced on lymphocytes, and on the cell membrane of hepatocytes, thus suggesting that an intrahepatic antigen-dependent lymphocyte-hepatocyte interaction occurs. Here we report the pattern of expression of several additional molecules known to participate in nonspecific cell-cell adhesion preceding alloantigen recognition i.e., the beta 1 chain of integrins (CD29) and the isoforms of the leukocyte common antigen CD45RA and CD45RO.


METHODS
Frozen liver samples from 38 patients with advanced ALD were examined immunohistochemically by the avidin-biotin-peroxidase complex method using monoclonal antibodies. Nine patients with alcoholic fatty liver and six patients with only hepatitis C infection were included as controls and studied in a similar manner.


RESULTS
CD29 was strongly expressed on the cell membrane of hepatocytes in 18/20 patients with cirrhosis, in 17/18 with alcoholic hepatitis without cirrhosis, in 5/9 of fatty liver and in all six with hepatitis C. CD45RA was present in 5/18 cases of alcoholic hepatitis and in 3/20 cases of cirrhosis on the hepatocytes plasma membrane, in none of the controls, and rarely on lymphocytes. CD45RO was expressed on the surface of lymphocytes in 14/18 cases of alcoholic hepatitis, 13/20 patients with cirrhosis, in 5/9 of fatty liver and in one with hepatitis C. The CD45RO lymphocytes were predominantly CD8 positive.


CONCLUSIONS
Our results indicate that in ALD the hepatocytes exhibit on their plasma membrane an enhanced expression of the beta 1 chain of the integrins and less commonly CD45RA. Furthermore, the expression of only CD45RO on the surface of lymphocytes favors the postulate that the intrahepatic lymphocytes in ALD are most likely of the "memory" type. The results of this study lend further support to the contention that a cell-cell contact precedes a cell-mediated mechanism in the pathogenesis of ALD.
Chedid
A
A
Department of Veterans Affairs Medical Centers, Cincinnati, Ohio.
Mendenhall
C L
CL
Moritz
T E
TE
French
S W
SW
Chen
T S
TS
Morgan
T R
TR
D015703:Antigens, CD / Q000032:analysis*; D001706:Biopsy; D006801:Humans; D007124:Immunoenzyme Techniques; D019012:Integrin beta1; D016023:Integrins / Q000032:analysis*; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male
D015703:Antigens, CD; D019012:Integrin beta1; D016023:Integrins; D017493:Leukocyte Common Antigens