Transforming growth factor-β-induced gene product, as a novel ligand of integrin αMβ2, 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-β-induced gene product (βig-h3/TGFBIp), as an extracellular matrix protein, mediates monocytes adhesion under both static and flow conditions mainly through integrin αMβ2. Fasciclin 1 domains of βig-h3/TGFBIp are responsible for the interaction with integrin αMβ2, 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 αMβ2. Intraperitoneal injection of βig-h3/TGFBIp promotes the recruitment of monocytes but not neutrophils. Our results demonstrate that βig-h3/TGFBIp produced at inflammatory sites is a novel chemoattractant for monocytes and interacts with integrin αMβ2 to serve as a substrate for their migration, suggesting that βig-h3/TGFBIp plays an important role in inflammation.