on September 30, 2004
Published online before print September 30, 2004, doi: 10.1161/01.ATV.0000146529.68729.8b
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on January 21, 2004
Accepted on September 8, 2004
Promotion of Leukocyte Adhesion by a Novel Interaction Between Vitronectin and the 
2 Integrin Mac-1 (
M2, CD11b/CD18)
Sandip M. Kanse *;
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.
* To whom correspondence should be addressed. E-mail: sandip.kanse{at}biochemie.med.uni-giessen.de.
Objective--The leukocyte integrin Mac-1 (
M
2, 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.
Key words: leukocyte adhesion • Mac-1 • integrins • vitronectin • CD18 • CD11b
This article has been cited by other articles:
 |
|
 |
|
  Y. Tsuruta, Y.-J. Park, G. P. Siegal, G. Liu, and E. Abraham Involvement of Vitronectin in Lipopolysaccaride-Induced Acute Lung Injury J. Immunol., November 15, 2007; 179(10): 7079 - 7086. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. U. Eisenhardt, M. Schwarz, N. Schallner, J. Soosairajah, N. Bassler, D. Huang, C. Bode, and K. Peter Generation of activation-specific human anti-{alpha}M{beta}2 single-chain antibodies as potential diagnostic tools and therapeutic agents Blood, April 15, 2007; 109(8): 3521 - 3528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zirlik, C. Maier, N. Gerdes, L. MacFarlane, J. Soosairajah, U. Bavendiek, I. Ahrens, S. Ernst, N. Bassler, A. Missiou, et al. CD40 Ligand Mediates Inflammation Independently of CD40 by Interaction With Mac-1 Circulation, March 27, 2007; 115(12): 1571 - 1580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pendu, V. Terraube, O. D. Christophe, C. G. Gahmberg, P. G. de Groot, P. J. Lenting, and C. V. Denis P-selectin glycoprotein ligand 1 and beta2-integrins cooperate in the adhesion of leukocytes to von Willebrand factor Blood, December 1, 2006; 108(12): 3746 - 3752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Barthel, N. N. Jarjour, D. F. Mosher, and M. W. Johansson Dissection of the Hyperadhesive Phenotype of Airway Eosinophils in Asthma Am. J. Respir. Cell Mol. Biol., September 1, 2006; 35(3): 378 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Van de Walle, K. Vanhoorelbeke, Z. Majer, E. Illyes, J. Baert, I. Pareyn, and H. Deckmyn Two Functional Active Conformations of the Integrin {alpha}2{beta}1, Depending on Activation Condition and Cell Type J. Biol. Chem., November 4, 2005; 280(44): 36873 - 36882. [Abstract] [Full Text] [PDF]
|
|