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Vasoactive intestinal peptide enhances phorbol myristate acetate-induced chemiluminescence in human lymphocytes
M A Lopez-Gonzalez1, J M Guerrero, M Lucas
1Departamento de Bioquímica Médica y Biología Molecular, Hospital Universitario Virgen Macarena, Facultad de Medicina, Sevilla, Spain.
Abstract:
Phorbol-myristate-acetate (PMA) induced in lymphocytes the production or reactive oxygen intermediates in a process which was stimulated by the presence of vasoactive intestinal peptide (VIP) in a dose-dependent response at VIP concentrations in the range 10(-11)-10(-8) M. The dissociation constant for the high-affinity receptors of VIP agreed with the ID50 of the activation of adenylate cyclase, and the ID50 for the stimulation by VIP of PMA-induced chemiluminescence, which were close to 0.2 nM VIP. Forskolin produced in lymphocytes an effect quite similar to VIP. A comparison of the response to VIP and forskolin of lymphocytes and monocytes showed that, in contrast to forskolin, VIP failed to induce the above described effect in monocytes. A possible mechanism involving protein kinase C, which is activated by PMA, and an intracellular signal linked to VIP receptors is pointed out. This study further supports a role for VIP as a mediator in the neuroimmune system.
Insights
Vasoactive intestinal peptide (VIP) enhances the production of reactive oxygen intermediates in lymphocytes, a process linked to the neuroimmune system. This VIP-induced effect in lymphocytes was not observed in monocytes.
Area of Science:
- Immunology
- Neuroendocrinology
- Cellular Signaling
Background:
- Vasoactive intestinal peptide (VIP) is a neuropeptide with known immunomodulatory functions.
- Phorbol-myristate-acetate (PMA) is a potent activator of protein kinase C and induces reactive oxygen intermediate (ROI) production in lymphocytes.
Purpose of the Study:
- To investigate the effect of VIP on PMA-induced ROI production in lymphocytes.
- To explore the potential role of VIP in the neuroimmune system.
Main Methods:
- Lymphocytes and monocytes were treated with PMA, VIP, and forskolin.
- Chemiluminescence was measured to quantify ROI production.
- Adenylate cyclase activity and VIP receptor binding were assessed.
Main Results:
- VIP dose-dependently stimulated PMA-induced ROI production in lymphocytes within a concentration range of 10(-11)-10(-8) M.
- The dissociation constant for high-affinity VIP receptors correlated with VIP's effect on adenylate cyclase and chemiluminescence (ID50 ≈ 0.2 nM).
- Forskolin mimicked VIP's effect in lymphocytes, but VIP did not induce a similar effect in monocytes.
Conclusions:
- VIP acts as a mediator in the neuroimmune system by modulating lymphocyte responses.
- A signaling pathway involving protein kinase C and intracellular signals linked to VIP receptors is proposed.
- VIP's specific action on lymphocytes, distinct from monocytes, highlights cell-type-specific immune modulation.