Membrane type 1-matrix metalloproteinase is involved in the migration of human monocyte-derived dendritic cells

Abstract

Dendritic cells (DC) are highly mobile APC. The trafficking of both immature and mature DC is crucial for their functions, which depends mainly on chemotactic attraction and matrix metalloproteinases (MMP) activity. MMP that are in a transmembrane form belong to membrane type (MT)-MMP, among which MT1-MMP has been shown to possess strong proteolytic activity that is capable of degrading extracellular matrix molecules. Although it is well established that MMP are zinc-dependent endopeptidases that collectively degrade most components of the extracellular matrix, relatively little is known about MT-MMP-mediated matrix degradation during DC migration. In this study, we showed that MT1-MMP was expressed in human monocyte-derived immature and mature DC by semi-quantitative reverse transcription PCR and western blotting analyses. Moreover, immunofluorescence microscopic studies showed that MT1-MMP was expressed on the membrane surface of DC. Blocking of MT1-MMP activity greatly reduced the invasion capacity of immature DC in Matrigel, whereas mature DC mobility was not affected. Taken together, our results show a novel functional link between MT1-MMP and DC motility and suggest that MT1-MMP may play an important role in modulating the migration of immature DC. © 2006 The Authors.