The protease-activated receptor-2 upregulates keratinocyte phagocytosis

The protease-activated receptor-2 (PAR-2) belongs to the family of seven tr ansmembrane domain receptors, which are activated by the specific enzgmatic cleavage of their extracellular amino termini. Synthetic peptides correspo nding to the tethered ligand domain (SLIGRL in mouse, SLIGKV in human) can activate PAR-2 without the need for receptor cleavage. PAR-2 activation is involved in cell growth, differentiation and inflammatory processes, and wa s shown to affect melanin and melanosome ingestion by human keratinocytes. Data presented here suggest that PAR-2 activation may regulate human kerati nocyte phagocytosis, PAR-2 activation by trypsin, SLIGRL or SLIGKV increase d the ability of keratinocytes to ingest fluorescently labeled microspheres or E. coli K-12 bioparticles, This PAR-2 mediated increase in keratinocyte phagocytic capability correlated with an increase in actin polymerization and alpha-actinin reorganization, cell surface morphological changes and in creased soluble protease activity. Moreover, addition of serine protease in hibitors downmodulated both the constitutive and the PAR-2 mediated increas es in phagocytosis, suggesting that serine proteases mediate this functiona l activity in keratinocytes, PAR-2 involvement in keratinocyte phagocytosis is a novel function for this receptor.