title: IFN-alpha2 induces leukocyte integrin redistribution, increased adhesion, and migration.
abstract: The human type I Interferon (IFN) family includes 14 closely related cytokines that are produced in response to viral and bacterial infections and mediate the progress of innate immune responses to adaptive immune protection, bind to a common receptor, and have qualitatively similar biologic activities. We have shown previously that IFN-alpha2 can induce human T cell chemotaxis, suggesting that type I IFNs may contribute to the development of an inflammatory environment. We here report that, in addition to promoting T cell chemotaxis, IFN-alpha2 enhances T cell adhesion to integrin ligands, which is associated with integrin clustering on the T cell surface and enhanced conjugate formation with dendritic cells. These effects were prevented by inhibition of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K). As type I IFN receptor is ubiquitously expressed, this analysis was extended to other human leukocyte populations, including granulocytes and B cells. All leukocyte populations analyzed displayed increased chemotaxis, integrin clustering, and increased integrin-mediated adhesion following exposure to IFN-alpha2, revealing a broad-spectrum proinflammatory activity. These findings have obvious implications for the role of type I IFNs in the development of inflammatory responses leading to the initiation of adaptive immunity.
authors.affiliation: Department of Immunology, Division of Medicine, Faculty of Medicine, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
authors.forename: George
authors.initials: G
authors.lastname: Avraamides
authors.forename: Chi-Yan
authors.initials: CY
authors.lastname: Ng
authors.forename: Rachel
authors.initials: R
authors.lastname: David
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.forename: Henrieta
authors.initials: H
authors.lastname: Fazekasova
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mirenda
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.forename: Laura
authors.initials: L
authors.lastname: Runkel
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.forename: Federica M
authors.initials: FM
authors.lastname: Marelli-Berg
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000276:immunology; D019743:Chemokines, CXC / Q000276:immunology; D002867:Chromones / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000276:immunology*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000276:immunology*; D007962:Leukocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009025:Morpholines / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: C483024:CCL5 protein, human; C515255:CXCL12 protein, human; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D002867:Chromones; C515256:Cxcl12 protein, mouse; D004791:Enzyme Inhibitors; D016023:Integrins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009025:Morpholines; D011994:Recombinant Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases