Annals of Biomedical Engineering

, Volume 37, Issue 4, pp 737–748

Kinetics of LFA-1 Mediated Adhesion of Human Neutrophils to ICAM-1—Role of E-Selectin Signaling Post-Activation

  • Omolola Eniola-Adefeso
  • Ryan B. Huang
  • C. Wayne Smith
Article

Abstract

LFA-1 and Mac-1 are the two integrins involved in the arrest and firm adhesion of neutrophils. LFA-1 plays a role in the early stage of cell arrest while Mac-1 stabilizes firm adhesion. Here, we further elucidated the kinetics of LFA-1 activation and its role in mediating neutrophil adhesion to ICAM-1 in the presence of E-selectin interaction. We confirm that LFA-1 activation to high affinity is transient in nature, decaying back to low affinity within 1 min after chemotactic stimulation. However, we show for the first time that this downshift in LFA-1 affinity does not return back to the low affinity state when E-selectin interaction is present and active, but rather E-selectin signals an intermediate LFA-1 conformation through PI3-Kinase that maintains an intermediate level of neutrophil firm adhesion. We further show that this E-selectin signaling is capable of returning LFA-1 to the intermediate affinity conformation outside the 1-min window previously reported for LFA-1 functionality. While our work confirms a role for PI3-Kinase in neutrophil firm adhesion, we show that PI3-Kinase may not be important in the initial transition from rolling to firm arrest (i.e. LFA-1 shift from low to high affinity conformation occurring within seconds of chemotactic stimulation).

Keywords

Leukocytes Inflammation CD18 Integrins PI3-Kinase FMLP IL8 

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Copyright information

© Biomedical Engineering Society 2009

Authors and Affiliations

  • Omolola Eniola-Adefeso
    • 1
  • Ryan B. Huang
    • 1
  • C. Wayne Smith
    • 2
  1. 1.Department of Chemical EngineeringUniversity of MichiganAnn ArborUSA
  2. 2.Section of Leukocyte Biology, Department of PediatricsBaylor College of MedicineHoustonUSA

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