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Blood, Vol. 95 No. 2 (January 15), 2000: pp. 592-601

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

P. Sriramarao, Richard G. DiScipio, Ronald R. Cobb, Myron Cybulsky, Greg Stachnick, Diego Castaneda, Mariano Elices, and David H. Broide

From the Laboratory of Immunology and Vascular Biology, La Jolla Institute for Experimental Medicine La Jolla, CA; Cytel Corporation, La Jolla, CA; Department of Biology, Tanabe Research Laboratories, San Diego, CA; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario; and Department of Medicine, University of California San Diego, La Jolla, CA.

The ability of the alpha 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 alpha 4beta 1 and alpha 4beta 7 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 beta 1 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)-1beta -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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