Transforming growth factor-beta-induced gene product, as a novel ligand of integrin alpha(M)beta(2), 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 (beta ig-h3/TGFBIp), as an extracellular matrix protein, mediates monocytes adhesion under both static and flow conditions mainly through integrin beta(M)beta 2. Fasciclin 1 domains of beta ig-h3/TGFBIp are responsible for the interaction with integrin alpha(M)beta 2, 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 alpha(M)beta(2) Intraperitoneal injection of beta ig-h3/TGFBIp promotes the recruitment of monocytes but not neutrophils. Our results demonstrate that beta ig-h3/TGFBIp produced at inflammatory sites is a novel chemoattractant for monocytes and interacts with integrin alpha(M)beta(2) to serve as a substrate for their migration, suggesting that beta ig-h3/TGFBIp plays an important role in inflammation. (C) 2007 Elsevier Ltd. All rights reserved.