Premium
Destruction of the hepatocyte junction by intercellular invasion of L eptospira causes jaundice in a hamster model of W eil's disease
Author(s) -
Miyahara Satoshi,
Saito Mitsumasa,
Kanemaru Takaaki,
Villanueva Sharon Y. A. M.,
Gloriani Nina G.,
Yoshida Shinichi
Publication year - 2014
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12085
Subject(s) - bone canaliculus , hamster , aspartate transaminase , jaundice , cholestasis , biology , alanine transaminase , hepatocyte , pathogenesis , cell junction , pathology , microbiology and biotechnology , immunology , alkaline phosphatase , cell , medicine , endocrinology , in vitro , anatomy , enzyme , biochemistry
Summary Weil's disease, the most severe form of leptospirosis, is characterized by jaundice, haemorrhage and renal failure. The mechanisms of jaundice caused by pathogenic L eptospira remain unclear. We therefore aimed to elucidate the mechanisms by integrating histopathological changes with serum biochemical abnormalities during the development of jaundice in a hamster model of W eil's disease. In this work, we obtained three‐dimensional images of infected hamster livers using scanning electron microscope together with freeze‐cracking and cross‐cutting methods for sample preparation. The images displayed the corkscrew‐shaped bacteria, which infiltrated the D isse's space, migrated between hepatocytes, detached the intercellular junctions and disrupted the bile canaliculi. Destruction of bile canaliculi coincided with the elevation of conjugated bilirubin, aspartate transaminase and alkaline phosphatase levels in serum, whereas serum alanine transaminase and γ‐glutamyl transpeptidase levels increased slightly, but not significantly. We also found in ex vivo experiments that pathogenic, but not non‐pathogenic leptospires, tend to adhere to the perijunctional region of hepatocyte couplets isolated from hamsters and initiate invasion of the intercellular junction within 1 h after co‐incubation. Our results suggest that pathogenic leptospires invade the intercellular junctions of host hepatocytes, and this invasion contributes in the disruption of the junction. Subsequently, bile leaks from bile canaliculi and jaundice occurs immediately. Our findings revealed not only a novel pathogenicity of leptospires, but also a novel mechanism of jaundice induced by bacterial infection.