VCAM-1 is more effective than MAdCAM-1 in supporting eosinophil rolling under conditions of shear flow.
The ability of the alpha4 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 alpha4beta1 and alpha4beta7 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 beta1 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. (Blood. 2000;95:592-601)
Sriramarao
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P
Laboratory of Immunology and Vascular Biology, La Jolla Institute for Experimental Medicine La Jolla, CA 92037, USA. rao@ljiem.org
DiScipio
R G
RG
Cobb
R R
RR
Cybulsky
M
M
Stachnick
G
G
Castaneda
D
D
Elices
M
M
Broide
D H
DH
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D001249:Asthma / Q000097:blood; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000494:pharmacology*; D066298:In Vitro Techniques; D039441:Integrin alpha4; D039641:Integrin beta Chains; D019012:Integrin beta1 / Q000097:blood / Q000276:immunology; D016023:Integrins / Q000097:blood / Q000276:immunology; D009088:Mucoproteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013314:Stress, Mechanical; D019010:Vascular Cell Adhesion Molecule-1 / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039641:Integrin beta Chains; D019012:Integrin beta1; D016023:Integrins; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; C091368:integrin beta7; D039441:Integrin alpha4