Modulation by Interferons of Human Neutrophilic Granulocyte Migration

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Abstract
The effect of various interferons (IFN) on neutrophilic granulocyte (PMN) random and directed migration is incompletely understood. We, therefore, investigated PMN migration with a novel micropore membrane technique. No chemotactic effect of either 10–10000 U/ml IFN-α or IFN-β, or 1–1000 U/ml IFN-γ was observed on PMN isolated from normal human venous blood. However, when present on both sides of the micropore membrane, all the IFN (1000 U/ml IFN-α and IFN-β, 100 U/ml IFN-γ) inhibited both random and directed migration toward zymosan-activated serum (ZAS). IFN-γ was the most potent inhibitory agent and produced an inhibition of about 30%. When the bacterial peptide fMLP was used as a chemoattractant, IFN-γ also depressed chemotaxis. Taking the reduced random migration of IFN-γ treated cells into account, however, chemotaxis per se—toward both ZAS and fMLP—was not significantly affected. Random migration and directed migration assessed simultaneously with PMN from the same donor were clearly correlated for both control and IFN-γ treated cells, suggesting that a general antimotility effect of IFN-γ might explain both reduced random migration and chemotaxis. The antimotility effect of IFN-γ was not dependent on protein synthesis or on tyrosine kinase activity. In fact, inhibition of tyrosine kinase with herbimycin A increased the ZAS-stimulated motility of both control and IFN-γ-inhibited PMN. In conclusion, our data indicate that IFN depress both random and directed PMN migration by mechanisms that do not involve protein synthesis or protein tyrosine kinase activity.

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