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)

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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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