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Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3904-3911
Eosinophil Tethering to Interleukin-4-Activated Endothelial Cells
Requires Both P-Selectin and Vascular Cell Adhesion Molecule-1
Kamala D. Patel
From the Department of Physiology and Biophysics, University of
Calgary, Calgary, Alberta, Canada.
We examined the mechanisms used by eosinophils to tether and
accumulate on interleukin-4 (IL-4)-stimulated human umbilical vein
endothelial cells (HUVECs) under flow conditions. As previously reported, HUVECs treated for 24 hours with 20 ng/mL IL-4 had increased expression of P-selectin and vascular cell adhesion molecule-1 (VCAM-1)
but not E-selectin. We found that eosinophils tethered and rolled on
IL-4-stimulated HUVECs at physiologic shear stresses. Eosinophil
rolling was quickly followed by firm adhesion. Treatment with either an
anti-P-selectin monoclonal antibody (MoAb) or an anti-VCAM-1 MoAb
decreased both eosinophil tethering and accumulation at 2 dyn/cm2. VCAM-1 interacts with  4-integrins expressed on
eosinophils. We found that an anti-4-integrin MoAb also blocked
eosinophil tethering and accumulation at 2 dyn/cm2. None of
these MoAbs alone had an impact on eosinophil accumulation at lower
shear stresses, but when either an anti-VCAM-1 or an anti-4-integrin MoAb was used in combination with an
anti-P-selectin MoAb, all eosinophil tethering and accumulation on
IL-4-stimulated HUVECs were blocked. This was true at both high and
low shear stresses. These data show that both P-selectin and VCAM-1 are required to tether eosinophils at high shear stresses, but at low shear
stresses these adhesion proteins can act independently to recruit
eosinophils to IL-4-stimulated HUVECs.
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