Proteasome activity is required for T lymphocyte aggregation after mitogen activation.
The proteasome is a multicatalytic complex of proteases involved in T lymphocyte proliferation and activation through multiple mechanisms. In this study, we investigated its role in lymphocyte aggregation. We found that blocking proteasome activity by a proteasome-specific inhibitor lactacystin (LAC) prevented clustering of T lymphocytes after stimulation with various mitogens. Expression of adhesion molecules ICAM-1 and LFA-1 at cell surfaces of activated T cells was decreased after treatment with LAC. Mechanisms by which the proteasome intervenes in the expression of these adhesion molecules were different. LAC inhibited ICAM-1 expression at the mRNA level, whereas LFA-1 inhibition was probably at a post-translational level. Downregulation of these molecules after proteasome inhibition likely contributes to the observed repression of T cell aggregation. Our results show that the proteasome plays an important role in cell-cell interaction during T cell activation.
Research Center, Notre-Dame Hospital, CHUM, University of Montreal, Montreal, Canada.
N
N
Kanaan
H
H
Luo
J
J
Wu
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002448:Cell Adhesion; D002449:Cell Aggregation; D002450:Cell Communication; D002455:Cell Division; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019041:L-Selectin / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology*
D018960:Hyaluronan Receptors; D016169:Lymphocyte Function-Associated Antigen-1; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; C067713:lactacystin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine