Integrin alpha 6 beta 4 mediates dynamic interactions with laminin.
We present here a novel form of dynamic adhesion in which both the integrin receptor and the ligand supporting dynamic adhesion have been identified. Laminar flow assays showed that laminin supported attachment of alpha 6 beta 4-positive cells in the presence of fluid shear stress (tau < or = 2 dyn/cm2), indicating that these cells adhered to laminin within a fraction of a second. Further increases in flow rate (3.5 dyn/cm2 < or = tau < or = 100 dyn/cm2) initiated rolling of attached cells in the direction of flow, suggesting that rapidly formed adhesion is reversible and repeatable. Laminin fragment E8, which interacts with alpha 6 integrins, supported dynamic attachment and rolling but extracellular matrix glycoprotein fibronectin did not. In cell lines that express alpha 6 beta 4 but not alpha 6 beta 1 an anti-alpha 6 monoclonal antibody inhibited attachment to laminin in the presence of flow and following 5 minutes of static incubation. Infusion of this antibody onto cells adherent to laminin-coated slides led to rapid detachment of cells from the substratum. An anti-beta 1 monoclonal antibody diminished adhesion strength following static incubation but did not inhibit rapid attachment and flow-initiated rolling. These results indicate that in some alpha 6 beta 4-expressing epithelial and carcinoma cell lines, integrin alpha 6 beta 4 mediates rapidly formed dynamic interactions with laminin.
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Department of Mechanical Engineering, Catholic University of America, Washington, DC 20064.
Kleinman
H K
HK
Wu
S
S
Mercurio
A M
AM
Byers
S W
SW
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D006801:Humans; D039161:Integrin alpha6beta4; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D011233:Precipitin Tests; D012212:Rheology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D039161:Integrin alpha6beta4; D016023:Integrins; D007797:Laminin