Inhibition of Human Neutrophil Functions by Sulfated and Nonsulfated Cholecystokinin Octapeptides

Abstract

Carrasco, M., M. Del Rio, A. Hernanz and M. De La Fuente. Inhibition of human neutrophil functions by sulfated and nonsulfated cholecystokinin octapeptides. Peptides 18(3) 415–422, 1997.—The effects of CCK-8s and desulfated CCK-8 at concentrations ranging from 10−14 to 10−6M 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 10−8M, 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 10−10M. 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.