Regulation of thymic development by neprilysin inhibition.
Development of T lymphocyte is regulated by both thymocyte-stromal cell interactions and production of soluble factors such as cytokines, peptides and hormones. The local concentration of active biological peptides is regulated by a specialized family of enzymes expressed at the cell surface, the ectopeptidases. We found that treatment of fetal thymic organ cultures (FTOC) with the specific CD10 (endopeptidase 24.11) inhibitor, (N-(3-[(hydroaxyamino)carbonyl]-2-benzylidene-1-oxopropyl]-N-glyci ne), RB25 results in a marked delay in thymocyte differentiation. RB25 causes a significant decrease in the number of DP (CD4+CD8+) cells in favor of the TN (TcR alpha beta-CD4-CD8-) population. RB25 also blocks T lymphocyte differentiation in FTOC when preinjected into pregnant mice. Finally, RB25 was found to essentially affect the CD44+CD25- and CD44-CD25- thymocytes in "in vitro" and "in vivo" experiments after 2 days FTOC. Thus, a selective and stable endopeptidase 24.11 inhibitor impairs T cell development, an observation in agreement with the involvement of the CD10 antigen in early T cell development.
Guérin
S
S
CJF INSERM 9605, Faculté de Médecine, Nice, France.
Auberger
P
P
D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000502:physiology*; D009924:Organ Culture Techniques; D011247:Pregnancy; D013950:Thymus Gland / Q000196:embryology* / Q000502:physiology
D001597:Benzylidene Compounds; D004791:Enzyme Inhibitors; C108920:RB25 compound; D015260:Neprilysin; D005998:Glycine