Open Access Research

Cellular turnover and expression of hypoxic-inducible factor in acute acalculous and calculous cholecystitis

Merja Vakkala1, Jouko J Laurila1, Juha Saarnio2, Vesa Koivukangas2, Hannu Syrjälä3, Tuomo Karttunen4, Ylermi Soini4 and Tero I Ala-Kokko1*

Author Affiliations

1 Department of Anesthesiology, Division of Intensive Care, Oulu University Hospital, Kajaanintie 52, Oulu, Finland, FIN-90029

2 Department of Surgery, Oulu University Hospital, Kajaanintie 52, Oulu, Finland, FIN-90029

3 Department of Infection Control, Oulu University Hospital, Kajaanintie 52, Oulu, Finland, FIN-90029

4 Department of Pathology, Oulu University, Kajaanintie 50, Oulu, Finland, FIN-90029

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Critical Care 2007, 11:R116  doi:10.1186/cc6170

Published: 31 October 2007

Abstract

Introduction

Epithelial corrective and destructive mechanisms have not been studied in inflammatory gallbladder disease.

Methods

Epithelial apoptosis, cell proliferation and expression of hypoxia-inducible factor (HIF)-1α were compared in gallbladders from patients with acute acalculous cholecystitis (AAC; n = 30) and acute calculous cholecystitis (ACC; n = 21), and from patients undergoing surgery for other reasons (normal gallbladders; n = 9), which were removed during open cholecystectomy. The immunohistochemical stains included antibodies to Ki-67 (proliferation), M30 (apoptosis) and HIF-1α. Proliferation and apoptosis were expressed as percentages of positive cells. HIF-1α expression was expressed as absent, weak, or strong.

Results

Apoptosis (median [25th to 75th percentile]) was significantly increased in AAC (1.31% [0.75% to 1.8%], P < 0.001) and ACC (1.10% [0.63% to 1.64%], P = 0.001), compared with control samples (0.20% [0.07% to 0.45%]. The proliferation rate was significantly increased in AAC (8.0% [4.0% to 17.0%], P < 0.001) and ACC (14% [7.5% to 26.5%], P = 0.001) compared with control samples (1.0% [1.0% to 3.0%]). Strong HIF-1α staining was observed in 57% of AAC, in 100% of ACC and in 44% of control specimens (P < 0.001). Intense HIF-1α expression was associated with increased cell proliferation (P = 0.002).

Conclusion

Cell proliferation and apoptosis were increased in AAC and ACC, as compared with normal gallbladders. Expression of HIF-1α was lower in AAC than in ACC.