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, H.S., Morrison, V.L. , Conneely, M., Campbell, P.A., McGloin, D., Kliche, S., Watts, C., Prescott, A. and Fagerholm, S.C. (2013) 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. Journal of Biological Chemistry, 288(21), pp. 14698-14708. (doi:10.1074/jbc.M112.430918) (PMID:23585567) (PMCID:PMC3663495)

Lek, H.S., Morrison, V.L. , Conneely, M., Campbell, P.A., McGloin, D., Kliche, S., Watts, C., Prescott, A. and Fagerholm, S.C. (2013) 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. Journal of Biological Chemistry, 288(21), pp. 14698-14708. (doi:10.1074/jbc.M112.430918) (PMID:23585567) (PMCID:PMC3663495)

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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 leukocyte function-associated antigen-1 (LFA-1) regulation in primary murine effector T cells. These cells have high LFA-1 integrin expression and display high spontaneous binding to intercellular adhesion molecule-1 (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 (0.5–20-s contact time). The maximum unbinding force for this interaction was ∼140 piconewtons at 0.5-s contact time, increasing to 580 piconewtons at 20-s contact time. Also, the total work required to disrupt the interaction increased over the 20-s contact time, indicating LFA-1-mediated adhesion strengthening in primary effector T cells over a very quick time frame. 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Morrison, Dr Vicky
Authors: Lek, H.S., Morrison, V.L., Conneely, M., Campbell, P.A., McGloin, D., Kliche, S., Watts, C., Prescott, A., and Fagerholm, S.C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Biological Chemistry
Journal Abbr.:J Biol Chem.
Publisher:American Society for Biochemistry and Molecular Biology, Inc.
ISSN:0021-9258
ISSN (Online):1083-351X

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