INHIBITION OF HUMAN NEUTROPHIL FUNCTIONS BY SULFATED AND NONSULFATED CHOLECYSTOKININ OCTAPEPTIDES

The effects of CCK-8s and desulfated CCK-8 at concentrations ranging f rom 10-(14) to 10(-6) M were studied in vitro on several functions of human peripheral neutrophils: adherence to substrate, mobility (sponta neous and directed by a chemical gradient or chemotaxis), ingestion of inert particles (latex beads) or cells (Candida albicans), and produc tion of superoxide anion measured by the nitroblue tetrazolium reducti on test. The effect of CCK-8s on intracellular levels of cAMP was inve stigated as well as the implication of calcium in the action of CCK-8s on phagocytic function using stimulants and inhibitors of both intrac ellular and extracellular calcium channels. The two peptides, at conce ntrations from 10-(12) to 10(-8) M, inhibited significantly both mobil ity and ingestion capacities and increased adherence to substrate. A d ose-response relationship was observed with a maximum inhibition of ne utrophil functions at 10(-10) M. CCK-8s and desulfated CCK-8 induced i n these cells a significant, but transient, increase of cAMP levels at 60 s. Moreover, CCK-8s was found to inhibit completely the stimulatio n of latex bead phagocytosis in neutrophils produced by the calcium io nophore A23187. These results suggest that CCK-8 is a negative modulat or of several neutrophil functions and that the inhibition of these ac tivities could be carried out through an increase of the intracellular cAMP levels and a decrease of the extracellular calcium input. (C) 19 97 Elsevier Science Inc.