DECREASED NEUTROPHIL INFILTRATION IN THE PANCREAS AND LUNGS OF HSP70 TRANSGENIC MICE DURING CAERULEIN-INDUCED PANCREATITIS.

Abstract

Exposure of organisms to initial sub-lethal stress leads to synthesis of heat shock proteins (HSPs). These stress proteins confer protection against subsequent severe stress. HSP70 is a well-studied member of stress proteins. We have shown earlier that overexpression of this protein by thermal and nonthermal stress is protective in pancreatitis and associated lung injury. Induction of thermal and non-thermal stress can modulate a number of other events in the tissue; therefore, studies using transgenic animals are necessary to delineate the role of this important stress protein in reduction of pancreatitis. After the initial injury in the tissue, neutrophil infiltration contributes significantly to the development of pancreatitis and associated lung injury. In the present study, we have evaluated neutrophil sequestration and tissue injury in HSP70 transgenic mice during careulein induced pancreatitis. Methods: Transgenic mice with human HSP70 were generated using a construct containing HSP70 under the control of CMV promoter. Pancreatitis was induced in wild type and transgenic mice by administration of caerulein (50 μg/kg/hourly for 12 hours). Pancreas and lungs were collected from wild type and transgenic animals and neutrophil sequestration was studied by measuring myeloperoxidase activity and histological alterations and tissue injury were quantitated by morphometry. Results: There was significantly less neutrophil infiltration both in the pancreas (control 3.5±2.1; wild type 540.5±94.5; HSP-transgenic 105.4±26.1) and lungs (control 338.14±133.4; wild type 1530.1±284.9; HSP-transgenic 808.9±226.7) of the HSP70-transgenic mice as compared to wild type animals following caerulein administration. Further, intra-acinar vacuolization, acinar cell necrosis and interstitial edema were reduced in the transgenic animals in comparison to wild type mice. Conclusion: These results suggest that HSP70 overexpression has a protective role in pancreatitis and can play a critical role in reducing the associated lung injury.