An in vitro model for the study of phagocytosis of damaged hepatocytes by rat Kupffer cells.
OBJECTIVE
One function of Kupffer cells is the phagocytosis of nonviable hepatocytes. Our aims were to develop a model for phagocytosis of damaged hepatocytes by rat Kupffer cells in vitro, and to characterise prostaglandin E2 (PGE2), prostacyclin (PGI), and tumour necrosis factor-alpha (TNF) production in this model.


METHODS
Kupffer cells were incubated alone or with damaged hepatocytes for up to 18 h, then washed and cultured for up to 66 h. To compare mediator responses produced during inert particle phagocytosis, Kupffer cells were also incubated with latex beads.


RESULTS
Phagocytic uptake of hepatocyte debris was confirmed in at least 50% of Kupffer cells. A dissociation between TNF and PGI responses was found for both latex beads and damaged hepatocytes, such that a TNF secretory response was not triggered by either stimulus whereas PGI production was increased for both. Although phagocytosis of beads increased PGE2 production, phagocytosis of hepatocytes did not.


CONCLUSIONS
Phagocytosis of damaged hepatocytes by Kupffer cells results in the production of PGI but not PGE2 or TNF.
Olynyk
J K
JK
University Department of Medicine, Fremantle Hospital, Western Australia.
Britton
R S
RS
Stephenson
A H
AH
Leicester
K L
KL
O'Neill
R
R
Bacon
B R
BR
D000818:Animals; D003470:Culture Media / Q000737:chemistry; D015232:Dinoprostone / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D006358:Hot Temperature / Q000009:adverse effects; D066298:In Vitro Techniques; D007728:Kupffer Cells / Q000502:physiology* / Q000648:ultrastructure; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010587:Phagocytosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D003470:Culture Media; D014409:Tumor Necrosis Factor-alpha; D011464:Epoprostenol; D015232:Dinoprostone