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Lookup NU author(s): Dr Michael Gray,
Professor Barry Argent
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Aim: To examine the effect of acute infection caused by herpesvirus (pseudorabies virus, PRV) on pancreatic ductal secretion. Methods: The virulent Ba-DupGreen (BDG) and non-virulent Ka-RREp0lacgfp (KEG) genetically modified strains of PRV were used in this study and both of them contain the gene for green fluorescent protein (GFP). Small intra/interlobular ducts were infected with BDG virus (107 PFU/mL for 6 h) or with KEG virus (1010 PFU/mL for 6 h), while non-infected ducts were incubated only with the culture media. The ducts were then cultured for a further 18 h. The rate of HCO3- secretion [base efflux -J(B-)] was determined from the buffering capacity of the cells and the initial rate of intracellular acidification (1) after sudden blockage of basolateral base loaders with dihydro-4,4,-diisothiocyanatostilbene-2,2,-disulfonic acid (500 μmol/L) and amiloride (200 μmol/L), and (2) after alkali loading the ducts by exposure to NH4Cl. All the experiments were performed in HCO3--buffered Ringer solution at 37 °C (n = 5 ducts for each experimental condition). Viral structural proteins were visualized by immunohistochemistry. Virally-encoded GFP and immunofluorescence signals were recorded by a confocal laser scanning microscope. Results: The BDG virus infected the majority of accessible cells of the duct as judged by the appearance of GFP and viral antigens in the ductal cells. KEG virus caused a similarly high efficiency of infection. After blockage of basolateral base loaders, BDG infection significantly elevated -J(B-) 24 h after the infection, compared to the non-infected group. However, KEG infection did not modify -J(B-). After alkali loading the ducts, -J(B-) was significantly elevated in the BDG group compared to the control group 24 h after the infection. As we found with the inhibitor stop method, no change was observed in the group KEG compared to the non-infected group. Conclusion: Incubation with the BDG or KEG strains of PRV results in an effective infection of ductal epithelial cells. The BDG strain of PRV, which is able to initiate a lytic viral cycle, stimulates HCO3- secretion in guinea pig pancreatic duct by about four- to fivefold, 24 h after the infection. However, the KEG strain of PRV, which can infect, but fails to replicate, has no effect on HCO3- secretion. We suggest that this response of pancreatic ducts to virulent PRV infection may represent a defense mechanism against invasive pathogens to avoid pancreatic injury. © 2005 The WJG Press and Elsevier Inc. All rights reserved.
Author(s): Heygi P, Ordog B, Rakonczai Jr Z, Takacs T, Lonovics J, Szabolcs A, Sari R, Toth A, Papp JG, Varro A, Kovacs MK, Gray MA, Argent BE, Boldogkoi Z
Publication type: Article
Publication status: Published
Journal: World Journal of Gastroenterology
ISSN (print): 1007-9327
ISSN (electronic): 1009-3079
Publisher: WJG Press
PubMed id: 16273613