Transforming growth factor-β-induced gene product, as a novel ligand of integrin α_Mβ₂, 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 α_Mβ₂. Fasciclin 1 domains of βig-h3/TGFBIp are responsible for the interaction with integrin α_Mβ₂, 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 α_Mβ₂. 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 α_Mβ₂ to serve as a substrate for their migration, suggesting that βig-h3/TGFBIp plays an important role in inflammation.