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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2251.)
© 2004 American Heart Association, Inc.

Vascular Biology

Promotion of Leukocyte Adhesion by a Novel Interaction Between Vitronectin and the ß₂ Integrin Mac-1 (_Mß₂, CD11b/CD18)

Sandip M. Kanse; Rachel L. Matz; Klaus T. Preissner; Karlheinz Peter

From the Institute for Biochemistry (S.M.K., R.L.M., K.T.P.), Justus-Liebig-University, Giessen, Germany; and the Department of Cardiology and Angiology (K.P.), Albert-Ludwigs-University, Freiburg, Germany.

Correspondence to Sandip Kanse, Institut für Biochemie, Fachbereich Medizin, Friedrichstraße 24, Justus-Liebig-Universität, D-35392 Giessen, Germany. E-mail sandip.kanse{at}biochemie.med.uni-giessen.de

Objective— The leukocyte integrin Mac-1 (_Mß₂, CD11b/CD18) binds a number of ligands and counter-receptors and thereby is a major determinant in regulation of leukocyte adhesion and extravasation. Vitronectin (VN) is an adhesion-promoting factor that is abundantly present as matrix molecule in vascular diseases such as atherosclerosis. Until now, only an indirect interaction between Mac-1 and VN via the urokinase receptor (urokinase plasminogen activator receptor) was known. We now propose that Mac-1 and VN can directly interact with each other.

Methods and Results— In an in vitro system with purified components, Mac-1 specifically bound the multimeric matrix form of VN but not the monomeric plasma form. Using various competitors, the interaction domains in Mac-1 and VN were localized. Mac-1–expressing but not untransfected Chinese hamster ovary cells adhered strongly on VN. Introduction of a GFFKR deletion in the _M subunit of Mac-1, which increases the constitutive activation of the integrin, led to increased adhesion on VN. Peripheral human blood neutrophils adhered and migrated on multimeric VN in a Mac-1–dependent manner.

Conclusions— These results show that there is a specific integrin-affinity–regulated interaction between Mac-1 and the matrix form but not the plasma form of VN that may significantly participate in leukocyte adhesion and extravasation.

Vitronectin promotes cell adhesion by binding to ß₁, ß₃, and ß₅ integrins and the urokinase receptor. We now demonstrate that vitronectin also binds directly to the leukocyte ß₂ integrin, Mac-1 (_Mß₂, CD11b/CD18), and this interaction mediates leukocyte adhesion and migration.

Key Words: leukocyte adhesion • Mac-1 • integrins • vitronectin • CD18 • CD11b

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