VCAM-1 is more effective than MAdCAM-1 in supporting eosinophil rolling under conditions of shear flow

Abstract

The ability of the 4 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 4β1 and 4β7 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.