Transforming growth factor-beta-induced gene product, as a novel ligand of integrin alphaMbeta2, promotes monocytes adhesion, migration and chemotaxis.
Monocyte recruitment from the blood in response to chemoattractant gradients is a key phenomenon in inflammation. Various extracellular matrix proteins, at the site of inflammation, have chemoattractant activity and mediate monocyte adhesion and migration as ligands of integrins. In this report, we demonstrate that transforming growth factor-beta-induced gene product (betaig-h3/TGFBIp), as an extracellular matrix protein, mediates monocytes adhesion under both static and flow conditions mainly through integrin alphaMbeta2. Fasciclin 1 domains of betaig-h3/TGFBIp are responsible for the interaction with integrin alphaMbeta2, not only enhances monocyte migration in both chemotactic and haptotactic manners but also mediates their transendothelial migration and subendothelial matrix invasion. These activities are also mediated through integrin alphaMbeta2. Intraperitoneal injection of betaig-h3/TGFBIp promotes the recruitment of monocytes but not neutrophils. Our results demonstrate that betaig-h3/TGFBIp produced at inflammatory sites is a novel chemoattractant for monocytes and interacts with integrin alphaMbeta2 to serve as a substrate for their migration, suggesting that betaig-h3/TGFBIp plays an important role in inflammation.
Kim
Ha-Jeong
HJ
Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, 101 Dongin-dong Jung-gu, Daegu 700-422, Republic of Korea.
Kim
In-San
IS
D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D042783:Endothelial Cells / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D017434:Protein Structure, Tertiary; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000494:pharmacology*; D000099222:betaIG-H3 Protein
D016326:Extracellular Matrix Proteins; D008024:Ligands; D016177:Macrophage-1 Antigen; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein