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Neutrophils can adhere via alpha4beta1-integrin under flow conditions
PH Reinhardt, JF Elliott and P Kubes
Immunology Research Group, University of Calgary, Alberta, Canada.
In this study we investigated the possibility that an alternative pathway
exists for neutrophil recruitment, namely an alpha4beta1- dependent
pathway. A parallel plate chamber was used to investigate whether
neutrophils could tether, roll, and adhere to tumor necrosis factor alpha
(TNF alpha)-stimulated endothelium via alpha4beta1. alpha4beta1-integrin
was induced on neutrophils using dihydrocytochalasin B and either an
endogenous (endothelial-derived) chemotactic agent or an exogenous
chemotactic molecule. alpha4beta1- expressing neutrophils could stably
adhere under shear force (2 dyne/cm2) to TNF alpha-stimulated endothelium
independent of the beta2- integrin. The firm adhesion was entirely
abolished by antibodies directed against either the alpha4 or
beta1-integrin subunits. However, the rolling interaction was not dependent
on alpha4beta1 but was abolished by antiselectin therapy. Neutrophils
expressing alpha4beta1 could also tether to the endothelium in the presence
of antiselectin therapy, but at shear stresses less than 2 dyne/cm2.
alpha4beta1- expressing neutrophils also tethered to and stably adhered (no
rolling) to VCAM-1- but not to ICAM-1-transfected L cells. The interaction
only occurred at shear stress less than 2 dyne/cm2. A cell line (Ramos)
known to express high quantities of alpha4beta1-integrin interacted with
VCAM-1-transfected L cells at very similar shear conditions.
alpha4beta1-expressing neutrophils were also able to adhere to a second
alpha4-integrin ligand, fibronectin; however, this interaction only
occurred under static conditions. These data suggest that, under certain
conditions, neutrophils can adhere independently of the beta2- integrin
pathway and adhere via the alpha4beta1-integrin. This study refutes the
concept that alpha4beta1-integrin adhesion is restricted to mononuclear
leukocytes and is not functional on human neutrophils.
Volume 89,
Issue 10,
pp. 3837-3846,
05/15/1997
Copyright © 1997 by The American Society of Hematology

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