MODULATION BY INTERFERONS OF HUMAN NEUTROPHILIC GRANULOCYTE MIGRATION

The effect of various interferons (HN) on neutrophilic granulocyte (PM N) random and directed migration is incompletely understood, We, there fore, investigated PMN migration with a novel micropore membrane techn ique, No chemotactic effect of either 10-10000 U/ml IFN-alpha or IFN-b eta, or 1-1000 U/ml IFN-gamma was observed on PMN isolated from normal human venous blood, However, when present on both sides of the microp ore membrane, all the IFN (1000 U/ml IFN-alpha and IFN-beta, 100 U/ml IFN-gamma) inhibited both random and directed migration toward zymosan -activated serum (ZAS), IFN-gamma was the most potent inhibitory agent and produced an inhibition of about 30%, When the bacterial peptide f MLP was used as a chemoattractant, IFN-gamma also depressed chemotaxis , Taking the reduced random migration of IFN-gamma treated cells into account, however, chemotaxis per se-toward both ZAS and fMLP-was not s ignificantly affected, Random migration and directed migration assesse d simultaneously with PMN from the same donor were clearly correlated for both control and IFN-gamma treated cells, suggesting that a genera l antimotility effect of IFN-gamma might explain both reduced random m igration and chemotaxis, The antimotility effect of IFN-gamma was not dependent on protein synthesis or on tyrosine kinase activity, In fact , inhibition of tyrosine kinase with herbimycin A increased the ZAS-st imulated motility of both control and IFN-gamma-inhibited PMN, In conc lusion, our data indicate that IFN depress both random and directed PM N migration by mechanisms that do not involve protein synthesis or pro tein tyrosine kinase activity.