Journal of Electron Microscopy Advance Access published online on October 12, 2009
Journal of Electron Microscopy, doi:10.1093/jmicro/dfp049
Dimethylthiourea pretreatment inhibits endotoxin-induced compound exocytosis in goblet cells and plasma leakage of rat small intestine
1 Department of Biological Sciences, National Sun Yat-Sen University, Taiwan
2 Department of Pathology, Kaohsiung Veterans General Hospital, Taiwan
3 Division of Urology, Long Chuan Veterans Hospital, Faculty of Biomedical Science, Taiwan
4 Environmental Biology, Kaohsiung Medical University, Taiwan and
5 Departments of Beauty Science and Nursing, Meiho Institute of Technology, Taiwan
* To whom correspondence should be addressed. E-mail: x0024{at}meiho.edu.tw
Intravenous application of a high dose of endotoxin, also called lipopoly-saccharide (LPS), results in endotoxemia in animals, that induces production of cytokines and free radicals, systemic inflammation and mucin discharge from mucous tissues. The present study was to investigate (1) whether LPS application increased goblet cell secretion by compound exocytotic activity in mucosal villi and crypts of rat small intestine, and (2) whether hydroxyl radicals were involved in LPS-induced compound exocytosis in goblet cells and plasma leakage. Scanning electron microscopy showed that the numbers of goblet cells undergoing compound exocytosis (cavitated goblet cells) per mm2 of ileal villus epithelium in rats 5 and 30 min after LPS (15 mg kg–1) were 693 ± 196 (N = 6) and 547 ± 213 (N = 6), respectively, which were 5.1 and 8.4 times (P < 0.05) the number of saline control. The percentage of villus cavitated goblet cell numbers, in both duodenum and ileum 5 min after LPS and in the ileum 30 min after LPS, increased significantly (P < 0.05). Pretreatment with dimethylthiourea (DMTU), a hydroxyl radical scavenger, decreased the number of cavitated goblet cells to saline control (P > 0.05). Morphometric analysis showed that the percentage of crypt epithelial area in the duodenum and ileum occupied by goblet cell mucin stores in the duodenum and ileum 30 min after LPS were 3.8 ± 0.2% (N = 6) and 6.9 ± 0.5 (N = 6), respectively reducing to one half the amount of control (P < 0.01). When DMTU was given prior to LPS the crypt goblet cell mucin stores and the amount of plasma leakage returned to the level of control. It is concluded that hydroxyl radicals were involved in the LPS-induced increase in compound exocytotic activity of goblet cells and the increase in plasma leakage during acute phases of inflammatory response in rat small intestine.
Keywords goblet cells, endotoxin, intestine, inflammation, mucins, hydroxyl radicals
Received 15 June 2009, accepted 9 September 2009