title: Modulation by interferons of human neutrophilic granulocyte migration.
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-alpha or IFN-beta, 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 micropore 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 fMLP 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 significantly affected. Random migration and directed migration assessed simultaneously with PMN from the same donor were clearly correlated for both control and IFN-gamma treated cells, suggesting that a general antimotility effect of IFN-gamma might explain both reduced random migration 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-stimulated motility of both control and IFN-gamma-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.
authors.affiliation: Department of Physiology, University of Oslo, Norway.
authors.forename: V
authors.initials: V
authors.lastname: Aas
authors.forename: K T
authors.initials: KT
authors.lastname: Lappegård
authors.forename: E M
authors.initials: EM
authors.lastname: Siebke
authors.forename: H B
authors.initials: HB
authors.lastname: Benestad
mesh_terms: D000704:Analysis of Variance; D016227:Benzoquinones; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D047029:Lactams, Macrocyclic; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D017828:Rifabutin / Q000031:analogs & derivatives
chemical_list: D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D011500:Protein Synthesis Inhibitors; D011809:Quinones; D011994:Recombinant Proteins; D017828:Rifabutin; D009240:N-Formylmethionine Leucyl-Phenylalanine; C020754:herbimycin; D007372:Interferons; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases