Inhibition of human neutrophil functions by sulfated and nonsulfated cholecystokinin octapeptides.
The effects of CCK-8s and desulfated CCK-8 at concentrations ranging from 10(-14) to 10(-6) M were studied in vitro on several functions of human peripheral neutrophils: adherence to substrate, mobility (spontaneous and directed by a chemical gradient or chemotaxis), ingestion of inert particles (latex beads) or cells (Candida albicans), and production of superoxide anion measured by the nitroblue tetrazolium reduction test. The effect of CCK-8s on intracellular levels of cAMP was investigated as well as the implication of calcium in the action of CCK-8s on phagocytic function using stimulants and inhibitors of both intracellular and extracellular calcium channels. The two peptides, at concentrations from 10(-12) to 10(-8) M, inhibited significantly both mobility and ingestion capacities and increased adherence to substrate. A dose-response relationship was observed with a maximum inhibition of neutrophil functions at 10(-10) M, CCK-8s and desulfated CCK-8 induced in these cells a significant, but transient, increase of cAMP levels at 60 s. Moreover, CCK-8s was found to inhibit completely the stimulation of latex bead phagocytosis in neutrophils produced by the calcium ionophore A23187. These results suggest that CCK-8 is a negative modulator of several neutrophil functions and that the inhibition of these activities could be carried out through an increase of the intracellular cAMP levels and a decrease of the extracellular calcium input.
Carrasco
M
M
Departamento de Biología Animal II (Fisiología Animal), Facultad de Ciencias Biológicas, Universidad Complutense de Madrid, Spain.
Del Rio
M
M
Hernanz
A
A
De la Fuente
M
M
D000328:Adult; D002110:Caffeine / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D000242:Cyclic AMP / Q000737:chemistry; D004357:Drug Synergism; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D007962:Leukocytes; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D016897:Respiratory Burst / Q000187:drug effects; D012433:Ryanodine / Q000494:pharmacology; D012844:Sincalide / Q000378:metabolism / Q000494:pharmacology*
D012433:Ryanodine; D002110:Caffeine; D004533:Egtazic Acid; D000242:Cyclic AMP; D012844:Sincalide