Secretory phospholipase A2 is required to produce histologic changes associated with gastroduodenal reflux in a murine model
| Autor: | Anirban Banerjee, Xianzhong Meng, Sagar S. Damle, David A. Fullerton, Fabia Gamboni-Robertson, Michael J. Weyant, Joseph C. Cleveland, Ashok N. Babu |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Pulmonary and Respiratory Medicine
Pathology medicine.medical_specialty Esophageal Neoplasms H&E stain Fluorescent Antibody Technique Sensitivity and Specificity Barrett Esophagus Mice Random Allocation Phospholipase A2 Metaplasia Biomarkers Tumor Animals Medicine Esophagus Probability Analysis of Variance Mice Inbred BALB C biology business.industry Biopsy Needle medicine.disease Immunohistochemistry Mice Inbred C57BL Esophageal Tissue Disease Models Animal Phospholipases A2 Cell Transformation Neoplastic medicine.anatomical_structure Gastroesophageal Reflux Tissue and Organ Harvesting biology.protein Duodenum GERD Surgery medicine.symptom business Cardiology and Cardiovascular Medicine Precancerous Conditions |
| Zdroj: | The Journal of Thoracic and Cardiovascular Surgery. 135(6):1220-1227 |
| ISSN: | 0022-5223 |
| DOI: | 10.1016/j.jtcvs.2007.10.080 |
| Popis: | Objective The earliest response of esophageal mucosa to gastric reflux is the development of oxidative damage and inflammation. These processes contribute to the development of metaplasia known as Barrett's esophagus, as well as the progression to malignancy. Secretory phospholipase A 2 is a mediator of inflammation with levels that are increased in Barrett's metaplasia and carcinoma when compared with levels in normal samples. Our goal is to determine the role of secretory phospholipase A 2 in the development of reflux-associated changes in the esophageal mucosa. Methods Secretory phospholipase A 2 –deficient mice (C57BL/6, n=5) and mice known to express high levels of secretory phospholipase A 2 (BALB/c, n=5) underwent side-to-side surgical anastomosis of the first portion of the duodenum and gastroesophageal junction, allowing exposure of esophageal mucosa to duodenal and gastric contents duodeno-gastroesophageal anastomosis. Control animals (n = 5) of each strain underwent laparotomy with esophagotomy and repair. Tissue was frozen in embedding medium. Hematoxylin and eosin staining and Ki67 and secretory phospholipase A 2 immunohistochemistry were used to evaluate esophageal tissue and its response to duodeno-gastroesophageal anastomosis. Results Immunofluorescent staining confirmed the absence of secretory phospholipase A 2 in C57BL/6 mice and its presence in BALB/c mice. Hematoxylin and eosin staining demonstrated significant thickening of the esophageal mucosa in response to gastroesophageal reflux in the presence of secretory phospholipase A 2 . Mice known to express high levels of secretory phospholipase A 2 also demonstrated increased numbers of proliferating cells. Secretory phospholipase A 2 –deficient mice were immune to the early changes induced by mixed reflux. Conclusions The presence of secretory phospholipase A 2 appears necessary for early histologic changes produced by exposure of the esophagus to gastroduodenal contents. This enzyme is identified as a promising target for evaluation of mechanisms of carcinogenesis and chemoprevention of esophageal carcinoma. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|