Lecithin: retinol acyltransferase protein is distributed in both hepatic stellate cells and endothelial cells of normal rodent and human liver.
BACKGROUND
To determine the extent to which hepatic stellate cell (HSC) activation contributes to liver fibrosis, it was found necessary to develop an alternative structural and functional stellate cell marker for in situ studies. Although several HSC markers have been reported, none of those are associated with particular HSC functions.


OBJECTIVE
The present study was undertaken to examine whether lecithin:retinol acyltransferase (LRAT), the physiological retinol esterification enzyme of the liver, is a potential and relevant tissue marker for HSC.


METHODS
An antibody specific to mouse and human LRAT was prepared based on the amino acid sequences. Antibodies to LRAT were used for immunohistochemical studies to assess the distribution of LRAT-positive cells in the liver with the aid of fluorescence and immunogold electron microscopy.


RESULTS
LRAT-positive cells were found to be confined in the space of Disse, corresponding with the location of desmin-positive HSC in rodent liver, also in human liver. Interestingly, LRAT-positive staining was also observed along the liver sinusoidal endothelial lining. Furthermore, immune electron microscopic studies revealed that LRAT was mainly distributed in HSC within the rough-endoplasmic reticulum (RER) and multivesicular bodies, whereas LRAT staining within the endothelial cells was largely confined to the perinuclear area and to some extent to the RER.


CONCLUSIONS
Evidence has been accumulated that LRAT might serve as an excellent alternative HSC marker for future structural and functional studies. Furthermore, the presence of LRAT in endothelial cells might suggest a currently unknown function of this enzyme in liver endothelial biology.
Department of Internal Medicine, Division of Gastroenterology and Hepatology, The Jikei University School of Medicine, Tokyo, Japan.
Keisuke
K
Nagatsuma
Yoshihiro
Y
Hayashi
Hiroshi
H
Hano
Hiroshi
H
Sagara
Kazuhiro
K
Murakami
Masaya
M
Saito
Takahiro
T
Masaki
Tomoe
T
Lu
Mitsugu
M
Tanaka
Hideaki
H
Enzan
Yoshio
Y
Aizawa
Hisao
H
Tajiri
Tomokazu
T
Matsuura
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase