Engulfment of necrotic acinar cells by pancreatic stellate cells inhibits pancreatic fibrogenesis.
OBJECTIVE
We have previously reported that pancreatic stellate cells (PSCs) have a phagocytic function. The aim of the present study was to investigate whether engulfment of necrotic acinar cells affects pancreatic fibrogenesis.


METHODS
Rat pancreatic acinar cells were incubated for 48 hours to induce necrosis, and PSCs were allowed to interact with them for 12 to 48 hours. Annexin V and propidium iodide staining or detection of DNA fragmentation was used to identify cell death.


RESULTS
A large number of necrotic acinar cells were engulfed by PSCs. When PSCs were exposed to necrotic acinar cells for 12 hours, the number of living PSCs was significantly lower than among the control PSCs, which were not exposed to necrotic acinar cells. DNA degradation was observed in PSCs that had ingested necrotic acinar cells, and they were Annexin V and propidium iodide positive, suggesting that engulfment of necrotic acinar cells induced PSC death. There was no difference between the concentrations of transforming growth factor-beta in the medium of the PSCs that had engulfed acinar cells and the medium of the control PSCs.


CONCLUSIONS
Engulfment of necrotic acinar cells by PSCs induces PSC death, suggesting that engulfment of necrotic acinar cells may inhibit the progression of fibrogenesis.
Tahara
Junko
J
Department of Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
Shimizu
Kyoko
K
Shiratori
Keiko
K
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D005355:Fibrosis; D008297:Male; D009336:Necrosis; D046790:Pancreas, Exocrine / Q000473:pathology*; D010586:Phagocytes / Q000378:metabolism / Q000473:pathology*; D010587:Phagocytosis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta