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, David H. Broide

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)592-601
Number of pages10
JournalBlood
Volume95
Issue number2
DOIs
StatePublished - Jan 15 2000

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