TY - JOUR
T1 - VCAM-1 is more effective than MAdCAM-1 in supporting eosinophil rolling under conditions of shear flow
AU - Sriramarao, P.
AU - Discipio, Richard G.
AU - Cobb, Ronald R.
AU - Cybulsky, Myron
AU - Stachnick, Greg
AU - Castaneda, Diego
AU - Elices, Mariano
AU - Broide, David H.
PY - 2000/1/15
Y1 - 2000/1/15
N2 - The ability of the α4 integrin counterligands vascular cell adhesion molecule (VCAM)-1 or mucosal addressin (MAd)-CAM-1 to support eosinophil rolling or firm adhesion under conditions of physiologic flow has not been delineated. Using a parallel plate flow chamber in vitro and intravital microscopy in vivo, we demonstrate that eosinophil rolling and adhesion on VCAM-1 is mediated by both α4β1 and α4β7 integrins. Eosinophils rolled equally efficiently on both VCAM-1 2 domain and VCAM-1 7 domain, suggesting that the N-terminal 2 domains of VCAM-1 are sufficient to support eosinophil rolling under conditions of flow. Furthermore, activation of the eosinophil β1 integrin with monoclonal antibody (mAb) 8A2 resulted in both resistance to shear stress-induced detachment from VCAM-1 in vitro and in stable arrest of rolling eosinophils on interleukin (IL)-1β-stimulated venules in vivo. Eosinophils rolled less efficiently on MAdCAM-1-than on VCAM-1-coated coverslips under conditions of flow. However, eosinophils firmly adhered as efficiently to MAdCAM-1 as to VCAM-1. Overall, these results demonstrate that both VCAM-1 and MAdCAM-1 can support eosinophil firm adhesion under conditions of flow. In contrast, VCAM-1 is significantly more efficient than MAdCAM-1 in supporting eosinophil rolling under conditions of flow.
AB - The ability of the α4 integrin counterligands vascular cell adhesion molecule (VCAM)-1 or mucosal addressin (MAd)-CAM-1 to support eosinophil rolling or firm adhesion under conditions of physiologic flow has not been delineated. Using a parallel plate flow chamber in vitro and intravital microscopy in vivo, we demonstrate that eosinophil rolling and adhesion on VCAM-1 is mediated by both α4β1 and α4β7 integrins. Eosinophils rolled equally efficiently on both VCAM-1 2 domain and VCAM-1 7 domain, suggesting that the N-terminal 2 domains of VCAM-1 are sufficient to support eosinophil rolling under conditions of flow. Furthermore, activation of the eosinophil β1 integrin with monoclonal antibody (mAb) 8A2 resulted in both resistance to shear stress-induced detachment from VCAM-1 in vitro and in stable arrest of rolling eosinophils on interleukin (IL)-1β-stimulated venules in vivo. Eosinophils rolled less efficiently on MAdCAM-1-than on VCAM-1-coated coverslips under conditions of flow. However, eosinophils firmly adhered as efficiently to MAdCAM-1 as to VCAM-1. Overall, these results demonstrate that both VCAM-1 and MAdCAM-1 can support eosinophil firm adhesion under conditions of flow. In contrast, VCAM-1 is significantly more efficient than MAdCAM-1 in supporting eosinophil rolling under conditions of flow.
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U2 - 10.1182/blood.v95.2.592
DO - 10.1182/blood.v95.2.592
M3 - Article
C2 - 10627468
AN - SCOPUS:0034650933
SN - 0006-4971
VL - 95
SP - 592
EP - 601
JO - Blood
JF - Blood
IS - 2
ER -