Receptor-independent mechanisms are involved in the priming of neutrophil's oxidase by vasoactive intestinal peptide.
Vasoactive intestinal peptide (VIP) primed the respiratory burst of human neutrophils induced by phorbol myristate acetate (PMA) and by the chemotactic peptide N-formyl-Met-Leu-Phe (fMLP). The sigmoidal-shaped curve of the priming effect of VIP differs for both agonist since the Hill coefficient was close to three in the case of neutrophil activation by fMLP whereas the corresponding value for PMA was close to one. The priming effect of VIP was enhanced when neutrophils were stimulated by FMLP in the presence of sphinganine, a protein kinase C inhibitor, at concentrations which almost abolished the response to PMA. VIP failed to increase resting cytosolic free calcium and to modify the transient increase in [Ca2+]i induced by fMLP. The described results point out that the mechanism of the priming of neutrophils by VIP is also independent of calcium and protein kinase C. The absence of VIP receptors in plasma membrane of neutrophils suggests that a receptor-independent mechanism modulates the agonist-triggered signaling pathway. The priming of neutrophils by VIP can not be considered as a pharmacological effect, as may be deduced from the required VIP concentration; it should be rather considered that the enhancement of the formation of reactive oxygen metabolites by VIP may be interesting in the understanding of the neuroimmune axis.
Pedrera
C
C
Departamento de Bioquímica Médica y Biología Molecular, Hospital Universitario Virgen Macarena, Facultad de Medicina, Sevilla, Spain.
Lucas
M
M
Bellido
L
L
López-González
M A
MA
D000001:Calcimycin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000097:blood; D019255:NADPH Oxidases; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000201:enzymology*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects*; D013004:Somatostatin / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D013004:Somatostatin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; C005682:safingol