Integrin Clustering Drives Phagocytosis Coupled to Collagenase 1 Induction Through RhoA GTPase and Superoxide Production

Abstract

Integrin-mediated phagocytosis in fibroblasts is associated to collagenase 1 induction when the particles are coated with high-affinity binding ligands. This study shows that the high density of ligand coating on the particle elicits RhoA-dependent particle uptake coupled to signal transduction. Integrin clustering induced by anti-integrin antibodies or cell surface-binding lectins is sufficient to trigger the pathway. The GTPase RhoA is recruited in response to integrin aggregation at the plasma membrane when uptake is inhibited at 4 degrees C and is necessary for particle engulfment, as function interference with the dominant negative mutant RhoAN19, but not with RacN17, abrogates particle ingestion. Phagocytosis driven by clustering is associated with signal transduction through a transient rise in cellular hydrogen peroxide production to induce a proinflammatory cascade leading to collagenase 1 induction.