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Departments of
*
Otolaryngology and
Immunology and Parasitology, Yokohama City University School of Medicine, Yokohama, Japan
This study examined the adhesive interaction of peripheral blood
monocytes with VCAM-1 and analyzed the effect of P-selectin binding to
monocytes on the adhesive interaction with VCAM-1 under flow
conditions. P-selectin glycoprotein ligand-1 is expressed on most
monocytes. Furthermore, most monocytes bind soluble P-selectin derived
from platelets. P-selectin binding to monocytes did not alter the
amount of expression of
4 integrin on monocytes.
However, the mean channel fluorescence value for binding Cy2-conjugated
soluble VCAM-1 to P-selectin-bound monocytes was slightly more than
that for binding Cy2-conjugated soluble VCAM-1 to untreated monocytes.
Under flow conditions, the number of P-selectin-bound monocytes bound
to VCAM-1 was much higher than that of untreated monocytes bound to
VCAM-1. These bindings were abolished by pretreatment of untreated
monocytes and P-selectin-bound monocytes with anti-VCAM-1 mAb or
anti-
4 integrin mAb. Furthermore, P-selectin binding
to monocytes increased shear resistance and thus increased the adhesive
strength of monocytes to VCAM-1. These findings indicate that
P-selectin binding to monocytes enhances the adhesive interaction of
monocytes with VCAM-1. It is suggested that P-selectin glycoprotein
ligand-1/P-selectin interaction and
4 integrin/VCAM-1
interaction can act sequentially in the adhesion cascade that regulates
monocyte trafficking to inflammatory and atherosclerotic
lesion.
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