Histomorphometric analysis of liver biopsies of treated patients with Gaucher disease type 1

Gaucher disease (GD) is an autosomal recessive lysosomal disorder caused by a disturbance in the metabolism of glucocerebroside in the macrophages. Most of its manifestations - hepatosplenomegaly, anemia, thrombocytopenia, and bone pain - are amenable to a macrophage-target therapy such as enzyme replacement. However, there is increasing evidence that abnormalities of the liver persist despite the specific GD treatment. In this work, we adapted histomorphometry techniques to the study of hepatocytes in GD using liver tissue of treated patients, developing the first morphometrical method for canalicular quantification in immunohistochemistry-stained liver biopsies, and exploring histomorphometric characteristics of GD. This is the first histomorphometric technique developed for canalicular analysis on histological liver biopsy samples.

The Effects of Cytochalasin B and Colchicine on Fine Structure of Bile Canaliculi and Hepatocytes in Mouse Liver / 대한해부학회지

Bile canaliculi is closely related to the cytoskeleton; actin filament web, microtubules and cytokeratin intermediate filaments. To understand how cytoskeletal alteration affects bile canalicular structure, the investigators injected cytochalasin B and colchicine into mice intraperitoneally to inhibit the polymerization of actin filaments and microtubules respectively, and observed the structural changes of bile canaliculi and hepatocytes with transmission and scanning electron microscopes. Bile canaliculi were dilatated and microvilli were decreased in number and length after injection of cytochalasin B and colchicine. Some bile canaliculi branched irregularly after colchicine treatment. Actin filament web in the canalicular ectoplasm was disrupted leaving granular zone after cytochalasin B treatment, but was intact after colchicine treatment. Intermediate filament bundles located at angles to the canalicular membrane appeared after colchicine treatment. Intercellular junctions delimiting bile canaliculi were intact after colchicine treatment, however were disrupted after cytochalsin B treatment. Focal junctions resembling desmosome were formed between microvilli after colchicine treatment. In both cytochalasin B and colchicine treated groups, lumen of rough endoplasmic reticulum were dilated, Golgi apparatus became prominent, and lipid droplets were appeared in the cytoplasm. These results suggest that both intact actin filaments and microtubules are necessary to keep the structural integrity of bile canaliculi.