Promotion of leukocyte adhesion by a novel interaction between vitronectin and the beta2 integrin Mac-1 (alphaMbeta2, CD11b/CD18).
OBJECTIVE
The leukocyte integrin Mac-1 (alphaMbeta2, 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.


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 alphaM 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.
Kanse
Sandip M
SM
Institute for Biochemistry, Justus-Liebig-University, Giessen, Germany. sandip.kanse@biochemie.med.uni-giessen.de
Matz
Rachel L
RL
Preissner
Klaus T
KT
Peter
Karlheinz
K
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism*; D016466:CHO Cells / Q000737:chemistry / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism; D014162:Transfection / Q000379:methods; D019096:Vitronectin / Q000378:metabolism*
D039481:CD11b Antigen; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D016028:Receptors, Leukocyte-Adhesion; D019096:Vitronectin