Expression of CCL21 and 5'-Nase on pancreatic lymphatics in nonobese diabetic mice.
OBJECTIVE
To obtain better insight into the modulation of lymphatic endothelial cells during the autoimmune process, alterations of the structures and histochemical features in the pancreatic lymphatics were studied in nonobese diabetic (NOD) mice.


METHODS
The expression of secondary lymphoid tissue chemokine (SLC/CCL21) and 5'-nucleotidase (5'-Nase) on pancreatic lymphatics was examined by histochemistry and immunoblot in NOD mice.


RESULTS
As insulitis developed, the increased expression of CCL21 and podoplanin on pancreatic lymphatics was consistent with the increased number of cytoplasmic protrusions and vesicles, whereas 5'-Nase activity of lymphatics seemed to become decreased. The expression of CCL21 protein also showed an age-dependent increase in NOD pancreas, even though it was undetectable in normal controls. During the period of severe infiltration, reaction products of CCL21 and podoplanin were detected in the nucleus and cytoplasm of lymphatic endothelial cells. Dendritic cells and T lymphocytes frequently penetrated through the slender walls of lymphatics and adhered to the lymphatic luminal surfaces, precipitating with few 5'-Nase particles. In contrast to wild-type NOD mice, complete Freund adjuvant administration reduced CCL21 expression in NOD pancreas, suppressing the entry of activated dendritic cells into lymphatics.


CONCLUSIONS
These findings suggest that CCL21 and 5'-Nase may be involved in the interaction between infiltrating cells and lymphatic vessels to induce the functional changes of lymphatic endothelial cells during insulitic and diabetic development.
Qu
Peng
P
Division of Morphological Analysis, Department of Anatomy, Biology and Medicine, Oita University Faculty of Medicine, Oita, Japan.
Ji
Rui-Cheng
RC
Kato
Seiji
S
D015720:5'-Nucleotidase / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose; D002450:Cell Communication / Q000502:physiology; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D005260:Female; D008208:Lymphatic System / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D001786:Blood Glucose; C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D015720:5'-Nucleotidase