Effects of substance P on human T cell function and the modulatory role of peptidase inhibitors.
Evidence has been presented for a modulatory role of surface peptidases on substance P-mediated immune responses. In this study, we first characterized the effects of substance P and its carboxy- and amino-terminal fragments on human lymphocyte proliferative responses to investigate whether peptidase inhibitors influence the effects of the neuropeptide. Substance P at 10(-7) M and the carboxy-terminal fragment SP(4-11) slightly enhanced the lymphocyte responses to phytohemagglutinin and concanavalin A. In contrast, the amino-terminal fragment SP(1-4) failed to have any positive effect. However, in the presence of dipeptidylpeptidase IV/CD26 and neutral endopeptidase/CD10 inhibitors (diprotin A and thiorphan, respectively), the effect of substance P on mitogen-induced proliferation was significantly increased. These data support the hypothesis that lymphocyte surface peptidases play a modulatory role in the effects of substance P on T cell function.
Covas
M J
MJ
Faculty of Medicine of Lisbon, Portugal.
Pinto
L A
LA
Victorino
R M
RM
D003208:Concanavalin A / Q000494:pharmacology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*
D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D010835:Phytohemagglutinins; D003208:Concanavalin A; D013373:Substance P; D018819:Dipeptidyl Peptidase 4; D015260:Neprilysin