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Vasoactive intestinal peptide inhibits fMLP-induced respiratory burst in human lymphocytes
L Bellido1, M A López-González, C Pedrera
1Departamento de Bioquímica Médica y Biolgía Molecular, Hospital Universitario Virgen Macarena, Facultad de Medicina, Sevilla, Spain.
Abstract:
N-Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) induced in lymphocytes the production of reactive oxygen intermediates in a process which was inhibited by the presence of Vasoactive Intestinal Peptide (VIP) in a dose-dependent response at VIP concentrations in the range 10(-10)-10(-7) M. The dissociation constant for the high-affinity receptors of VIP agrees with the ID50 of the activation of adenylate cyclase which are close to 0.2 nM VIP, whereas the ID50 for the inhibition by VIP of fMLP-induced chemiluminescence approaches to 5 nM VIP. Both IBMX and Forskolin produced in lymphocytes an inhibition of fMLP-induced chemiluminescence. The degree of inhibition was ascertained to be additive in the presence of the above indicated agents and suboptimal concentrations of VIP. The saturation by cAMP of its putative target, the regulatory subunit of protein kinase A, appears to be required for the onset of the inhibitory effect of VIP. This study provides evidence of the molecular signal, namely cAMP, which provokes an inhibitory effect on chemoatractant-stimulated human lymphocytes and further support a role for VIP as a mediator in the neuroimmune system.
Insights
Vasoactive Intestinal Peptide (VIP) inhibits reactive oxygen production in human lymphocytes stimulated by N-Formyl-Methionyl-Leucyl-Phenylalanine (fMLP). This effect is mediated by cyclic AMP (cAMP), highlighting VIP's role in the neuroimmune system.
Area of Science:
- Immunology
- Neuroendocrinology
- Cellular Signaling
Background:
- N-Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) stimulates human lymphocytes to produce reactive oxygen intermediates.
- Vasoactive Intestinal Peptide (VIP) is implicated as a mediator in the neuroimmune system.
Purpose of the Study:
- To investigate the inhibitory effect of VIP on fMLP-induced reactive oxygen intermediate production in lymphocytes.
- To elucidate the molecular mechanism underlying VIP's inhibitory action, focusing on cyclic AMP (cAMP) signaling.
Main Methods:
- Lymphocytes were stimulated with fMLP, and reactive oxygen intermediate production was measured.
- The effects of varying concentrations of VIP on fMLP-induced chemiluminescence were assessed.
- The role of cAMP and protein kinase A (PKA) in VIP's inhibitory mechanism was explored using agents like IBMX and Forskolin.
Main Results:
- VIP inhibited fMLP-induced chemiluminescence in a dose-dependent manner (10(-10)-10(-7) M).
- The inhibitory effect of VIP was found to be additive with IBMX and Forskolin, suggesting a common downstream pathway involving cAMP.
- Saturation of the regulatory subunit of protein kinase A by cAMP was identified as necessary for VIP's inhibitory effect.
Conclusions:
- Cyclic AMP (cAMP) acts as the molecular signal mediating VIP's inhibitory effect on chemoattractant-stimulated human lymphocytes.
- These findings provide further evidence for Vasoactive Intestinal Peptide (VIP) as a crucial mediator within the neuroimmune axis.