cAMP accumulation in T-cells inhibits anti-CD3 monoclonal antibody-induced actin polymerization.
The results presented in this report offer a novel explanation for how stimulation of the beta-adrenergic receptor (beta AR) inhibits the ability of T cells to proliferate after interaction with immobilized anti-CD3 monoclonal antibody (mAb). Accordingly, T cells binding to immobilized anti-CD3 mAb but not anti-CD4 mAb undergo time-dependent F-actin assembly with concomitant formation of pseudopodia. This process is completely inhibited in the presence of isoproterenol (ISO) indicating that stimulation of the beta AR on T cells interferes with the biochemical processes responsible for the assembly of actin. To confirm these observations, we quantitated the formation of F-actin in T cells stimulated with immobilized anti-CD3 mAb in the presence of cAMP elevating agents. The results show that stimulation of the beta AR on T-cells, as well as the addition of forskolin or dibutyryl cAMP, abrogates the formation of F-actin.
Selliah
N
N
Department of Microbiology and Immunology, University of Kentucky Medical Center, Lexington 40536-0084.
Bartik
M M
MM
Carlson
S L
SL
Brooks
W H
WH
Roszman
T L
TL
D000199:Actins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology*; D003994:Bucladesine / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000502:physiology
D000199:Actins; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; D007545:Isoproterenol