Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the relationship between insulitic development and function-structural changes of pancreatic lymphatics in non-obese diabetic (NOD) mice using combined 5'-nucleotidase (5'-Nase) enzyme histochemical and secondary lymphoid tissue chemokine (SLC/CCL21) immunohistochemical methods. Interlobular lymphatic vessels were positive for 5'-Nase throughout the pancreas, and dependent on both blood vessels and pancreatic ducts. Intralobular initial lymphatics were rare and occasionally ran in the neighbourhood of islets. During the non-insulitic stage, the 5'-Nase-reactive product was evenly distributed on the surface of lymphatic endothelial cells (LECs) with weak expression of CCL21. The activity of 5'-Nase on lymphatic vessels became slightly reduced as insulitis developed. The increasing blood glucose values appeared to be consistent with an increasing CCL21 expression by the endothelial lining, especially on the surface of LECs adjacent to the infiltrated islets and tissues. Lymphocytes and dendritic cells (DCs) were frequently located in the connective tissue, surrounding the lymphatic wall with deposition of 5'-Nase precipitates. As the infiltration became severe, lymphocytes and DCs accumulated within lymphatic vessels and expressed high levels of CCL21. The most significant finding was that many DCs adhered to lymphatic vessels, transmigrating via the thin and indented endothelial walls. The activity of 5'-Nase was increased on the adhesion surface between DCs (or lymphocytes) and LECs. The latter were characterized by open intercellular junctions and obvious cytoplasmic protrusions. These results suggest that LECs closely interact with DCs and lymphocytes, and play a key role in the migration of DCs and lymphocytes via lymphatic vessels during the pathological processes of insulitis in NOD mice.
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PMID:Histochemical analysis of lymphatic endothelial cells in the pancreas of non-obese diabetic mice. 1463 5

The present study has investigated the relationship between pancreatic lymphatics, infiltrating cells, and insulitic development after a single injection of complete Freund's adjuvant (CFA) given at an early age in the nonobese diabetic (NOD) mice. No CFA-treated NOD mice developed hyperglycemia, whereas most CFA-untreated mice died of diabetes at the age of 20-30 weeks. In untreated NOD mice, the increased infiltration of dendritic cells (DCs) and T-lymphocytes into the pancreatic islets appeared to be consistent with the increased expression of the secondary lymphoid chemokine (CCL21) and CD(31) by the endothelial cell lining of inter- and intralobular lymphatics. As the infiltration became severe, the reaction products of CCL21 and CD(31) were distributed in the nucleus and cytoplasm of lymphatic endothelial cells (LECs), through which DCs and T-lymphocytes migrated frequently. Administration of CFA reduced the number of infiltrating DCs and T-lymphocytes, but did not affect macrophage infiltration. The peri-insulitis occurred in numerous islets of CFA-treated NOD mice without the appearance of the intraislet infiltration and islet-associated lymphoid-like tissues. Furthermore, significant suppression of CCL21 and CD(31) was demonstrated on the infiltrating cells to the islets and islet-associated lymphatics. The abluminal endothelial cell lining of lymphatic vessels exhibited weaker immunoreactivity of CCL21 and CD(31) in comparison with the luminal surfaces. The reaction product of 5'-nucleotidase (5'-Nase) was evenly deposited on LECs, which were the absence of open junctions, cytoplasmic protrusions, and vesicles. CFA treatment influenced the migratory processes of the infiltrating cell, which were closely related with structural changes of pancreatic lymphatics and inhibited insulitic development. These findings suggest that in CFA-treated NOD mice, the suppression of insulitis and prevention of diabetes are secondary to the functional modulation of pancreatic lymphatics and infiltrating cells.
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PMID:Study on pancreatic lymphatics in nonobese diabetic mouse with prevention of insulitis and diabetes by adjuvant immunotherapy. 1538 76