Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.25 (triphosphatase)
 1,529 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dendritic cells (DCs) possess numerous dendrites that may be of great advantage to interaction with T cells. However, it has been poorly understood how the dendritic morphology of a DC is controlled. In the present study, using a murine spleen-derived DC line, we analyzed effects of CCR7 ligands, CCL19 and CCL21, on dendritic morphology. Mature DCs, but not immature DCs, showed vigorous migration to either CCL19 or CCL21. CCL19 also rapidly (within 30 minutes) induced marked extension of dendrites of mature DCs that was maintained at least for 24 hours. On the other hand, CCL21 failed to induce rapid dendritic extension, even though a modest dendritic extension of mature DCs, compared to that by CCL19, was induced 8 or 24 hours after treatment with CCL21. In addition, pretreatment with a high concentration of CCL21 significantly inhibited the rapid dendritic extension induced by CCL19. Thus, it is suggested that CCL19 and CCL21 exert agonistic and antagonistic influences on the initiation of dendritic extension of mature DCs. The CCL19-induced morphologic changes were completely blocked by Clostridium difficile toxin B that inhibits Rho guanosine triphosphatase proteins such as Rho, Rac, and Cdc42, but not by Y-27632, a specific inhibitor for Rho-associated kinase. These findings suggest that Rac or Cdc42 (or both), but not Rho, are involved in the CCL19-induced dendritic extension of mature DCs.
 ...
PMID:CCL19 induces rapid dendritic extension of murine dendritic cells. 1220 Mar 51

Although chemokines are well known to function in chemotaxis, additional roles for these molecules in the immune system are not well understood. Dendritic cells (DCs) developmentally regulate the expression of chemokine receptors to facilitate their migration from the peripheral tissues to regional lymph nodes. Expressions of CCR1 and CCR5 on immature DCs are down-regulated on maturation, whereas CCR7 is selectively expressed on mature DCs. In the present study, we examined the effects of CCL19 and CCL21, 2 CCR7 ligands, on endocytosis of fluorescein isothiocyanate (FITC)-dextran by murine DCs. Both CCL19 and CCL21 markedly induced rapid uptake of FITC-dextran by mature DCs but not immature DCs. In contrast, CCL3, a ligand of CCR1 and CCR5, induced rapid uptake of FITC-dextran by immature DCs but not mature DCs. CCL19-induced endocytosis could be completely blocked by Clostridium difficile toxin B, which inhibits the Rho guanosine triphosphatase proteins, Rho, Rac, and Cdc42. This process was not abrogated by Y-27632, a specific inhibitor of Rho-associated kinase. In addition, CCL19 rapidly enhanced Cdc42 and Rac activity in mature DCs. These findings demonstrate that certain chemokines induce rapid endocytosis in each relevant DC population. It is suggested that CCR7 ligands activate Cdc42 and Rac, thereby inducing the endocytosis in mature DCs.
 ...
PMID:CCR7 ligands induce rapid endocytosis in mature dendritic cells with concomitant up-regulation of Cdc42 and Rac activities. 1260 29