The spontaneously adhesive leukocyte function-associated antigen-1 (LFA-1) integrin in effector T cells mediates rapid actin- and calmodulin-dependent adhesion strengthening to ligand under shear flow

Hwee San Lek, Vicky L Morrison, Michael Conneely, Paul A Campbell, David McGloin, Stefanie Kliche, Colin Watts, Alan Prescott, Susanna C Fagerholm (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    Integrins in effector T cells are highly expressed and important for trafficking of these cells and for their effector functions. However, how integrins are regulated in effector T cells remains poorly characterized. Here, we have investigated effector T cell LFA-1 regulation in primary murine effector T cells. These cells have high LFA-1 integrin expression and display high spontaneous binding to ICAM-1 ligand under static conditions. In addition, these cells are able to migrate spontaneously on ICAM-1. Atomic force microscopy measurements showed that the force required for unbinding of integrin-ligand interactions increases over time (0.5s-20s contact time). The maximum unbinding force for this interaction was approximately 140pN at 0.5s contact time, increasing to 580pN at 20s contact time. Also the total work required to disrupt the interaction increased over the 20s contact time, indicating LFA-1-mediated adhesion strengthening in primary effector T cells over a very quick timeframe. Effector T cells adhered spontaneously to ICAM-1 under conditions of shear flow, in the absence of chemokine stimulation, and this binding was independent of protein kinase B/Akt and protein kinase C kinase activity, but dependent on calcium/calmodulin signaling and an intact actin cytoskeleton. These results indicate that effector T cell integrins are highly expressed and spontaneously adhesive in the absence of inside-out integrin signaling, but that LFA-1-mediated firm adhesion under conditions of shear flow requires downstream integrin signaling which is dependent on calcium/calmodulin and the actin cytoskeleton.
    Original languageEnglish
    Pages (from-to)14698-14708
    Number of pages11
    JournalJournal of Biological Chemistry
    Volume288
    Issue number21
    Early online date12 Apr 2013
    DOIs
    Publication statusPublished - 24 May 2013

    Fingerprint

    Lymphocyte Function-Associated Antigen-1
    T-cells
    Calmodulin
    Shear flow
    Integrins
    Adhesives
    Actins
    Adhesion
    Ligands
    T-Lymphocytes
    Intercellular Adhesion Molecule-1
    Actin Cytoskeleton
    Calcium
    Proto-Oncogene Proteins c-akt
    Calcium Signaling
    Atomic Force Microscopy
    Chemokines
    Atomic force microscopy

    Cite this

    @article{edf15c30f77b49d18b8687f87a851c5d,
    title = "The spontaneously adhesive leukocyte function-associated antigen-1 (LFA-1) integrin in effector T cells mediates rapid actin- and calmodulin-dependent adhesion strengthening to ligand under shear flow",
    abstract = "Integrins in effector T cells are highly expressed and important for trafficking of these cells and for their effector functions. However, how integrins are regulated in effector T cells remains poorly characterized. Here, we have investigated effector T cell LFA-1 regulation in primary murine effector T cells. These cells have high LFA-1 integrin expression and display high spontaneous binding to ICAM-1 ligand under static conditions. In addition, these cells are able to migrate spontaneously on ICAM-1. Atomic force microscopy measurements showed that the force required for unbinding of integrin-ligand interactions increases over time (0.5s-20s contact time). The maximum unbinding force for this interaction was approximately 140pN at 0.5s contact time, increasing to 580pN at 20s contact time. Also the total work required to disrupt the interaction increased over the 20s contact time, indicating LFA-1-mediated adhesion strengthening in primary effector T cells over a very quick timeframe. Effector T cells adhered spontaneously to ICAM-1 under conditions of shear flow, in the absence of chemokine stimulation, and this binding was independent of protein kinase B/Akt and protein kinase C kinase activity, but dependent on calcium/calmodulin signaling and an intact actin cytoskeleton. These results indicate that effector T cell integrins are highly expressed and spontaneously adhesive in the absence of inside-out integrin signaling, but that LFA-1-mediated firm adhesion under conditions of shear flow requires downstream integrin signaling which is dependent on calcium/calmodulin and the actin cytoskeleton.",
    author = "Lek, {Hwee San} and Morrison, {Vicky L} and Michael Conneely and Campbell, {Paul A} and David McGloin and Stefanie Kliche and Colin Watts and Alan Prescott and Fagerholm, {Susanna C}",
    year = "2013",
    month = "5",
    day = "24",
    doi = "10.1074/jbc.M112.430918",
    language = "English",
    volume = "288",
    pages = "14698--14708",
    journal = "Journal of Biological Chemistry",
    issn = "0021-9258",
    publisher = "American Society for Biochemistry and Molecular Biology",
    number = "21",

    }

    The spontaneously adhesive leukocyte function-associated antigen-1 (LFA-1) integrin in effector T cells mediates rapid actin- and calmodulin-dependent adhesion strengthening to ligand under shear flow. / Lek, Hwee San; Morrison, Vicky L; Conneely, Michael; Campbell, Paul A; McGloin, David; Kliche, Stefanie; Watts, Colin; Prescott, Alan; Fagerholm, Susanna C (Lead / Corresponding author).

    In: Journal of Biological Chemistry, Vol. 288, No. 21, 24.05.2013, p. 14698-14708.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The spontaneously adhesive leukocyte function-associated antigen-1 (LFA-1) integrin in effector T cells mediates rapid actin- and calmodulin-dependent adhesion strengthening to ligand under shear flow

    AU - Lek, Hwee San

    AU - Morrison, Vicky L

    AU - Conneely, Michael

    AU - Campbell, Paul A

    AU - McGloin, David

    AU - Kliche, Stefanie

    AU - Watts, Colin

    AU - Prescott, Alan

    AU - Fagerholm, Susanna C

    PY - 2013/5/24

    Y1 - 2013/5/24

    N2 - Integrins in effector T cells are highly expressed and important for trafficking of these cells and for their effector functions. However, how integrins are regulated in effector T cells remains poorly characterized. Here, we have investigated effector T cell LFA-1 regulation in primary murine effector T cells. These cells have high LFA-1 integrin expression and display high spontaneous binding to ICAM-1 ligand under static conditions. In addition, these cells are able to migrate spontaneously on ICAM-1. Atomic force microscopy measurements showed that the force required for unbinding of integrin-ligand interactions increases over time (0.5s-20s contact time). The maximum unbinding force for this interaction was approximately 140pN at 0.5s contact time, increasing to 580pN at 20s contact time. Also the total work required to disrupt the interaction increased over the 20s contact time, indicating LFA-1-mediated adhesion strengthening in primary effector T cells over a very quick timeframe. Effector T cells adhered spontaneously to ICAM-1 under conditions of shear flow, in the absence of chemokine stimulation, and this binding was independent of protein kinase B/Akt and protein kinase C kinase activity, but dependent on calcium/calmodulin signaling and an intact actin cytoskeleton. These results indicate that effector T cell integrins are highly expressed and spontaneously adhesive in the absence of inside-out integrin signaling, but that LFA-1-mediated firm adhesion under conditions of shear flow requires downstream integrin signaling which is dependent on calcium/calmodulin and the actin cytoskeleton.

    AB - Integrins in effector T cells are highly expressed and important for trafficking of these cells and for their effector functions. However, how integrins are regulated in effector T cells remains poorly characterized. Here, we have investigated effector T cell LFA-1 regulation in primary murine effector T cells. These cells have high LFA-1 integrin expression and display high spontaneous binding to ICAM-1 ligand under static conditions. In addition, these cells are able to migrate spontaneously on ICAM-1. Atomic force microscopy measurements showed that the force required for unbinding of integrin-ligand interactions increases over time (0.5s-20s contact time). The maximum unbinding force for this interaction was approximately 140pN at 0.5s contact time, increasing to 580pN at 20s contact time. Also the total work required to disrupt the interaction increased over the 20s contact time, indicating LFA-1-mediated adhesion strengthening in primary effector T cells over a very quick timeframe. Effector T cells adhered spontaneously to ICAM-1 under conditions of shear flow, in the absence of chemokine stimulation, and this binding was independent of protein kinase B/Akt and protein kinase C kinase activity, but dependent on calcium/calmodulin signaling and an intact actin cytoskeleton. These results indicate that effector T cell integrins are highly expressed and spontaneously adhesive in the absence of inside-out integrin signaling, but that LFA-1-mediated firm adhesion under conditions of shear flow requires downstream integrin signaling which is dependent on calcium/calmodulin and the actin cytoskeleton.

    UR - http://www.scopus.com/inward/record.url?scp=84878231569&partnerID=8YFLogxK

    U2 - 10.1074/jbc.M112.430918

    DO - 10.1074/jbc.M112.430918

    M3 - Article

    VL - 288

    SP - 14698

    EP - 14708

    JO - Journal of Biological Chemistry

    JF - Journal of Biological Chemistry

    SN - 0021-9258

    IS - 21

    ER -