The protease-activated receptor-2 upregulates keratinocyte phagocytosis.
The protease-activated receptor-2 (PAR-2) belongs to the family of seven transmembrane domain receptors, which are activated by the specific enzymatic cleavage of their extracellular amino termini. Synthetic peptides corresponding 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 was shown to affect melanin and melanosome ingestion by human keratinocytes. Data presented here suggest that PAR-2 activation may regulate human keratinocyte phagocytosis. PAR-2 activation by trypsin, SLIGRL or SLIGKV increased 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 *-actinin reorganization, cell surface morphological changes and increased soluble protease activity. Moreover, addition of serine protease inhibitors downmodulated both the constitutive and the PAR-2 mediated increases in phagocytosis, suggesting that serine proteases mediate this functional activity in keratinocytes. PAR-2 involvement in keratinocyte phagocytosis is a novel function for this receptor.
Johnson & Johnson-Consumer Products Worldwide, Skin Research Center, Skillman, NJ 08558, USA.
E R
ER
Sharlow
C S
CS
Paine
L
L
Babiarz
M
M
Eisinger
S
S
Shapiro
M
M
Seiberg
D000185:Actinin / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D016667:Bacterial Capsules; D002460:Cell Line; D002462:Cell Membrane / Q000648:ultrastructure; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D008863:Microspheres; D009842:Oligopeptides / Q000494:pharmacology; D010587:Phagocytosis; D011135:Polysaccharides, Bacterial / Q000378:metabolism; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000502:physiology*; D012697:Serine Endopeptidases / Q000187:drug effects / Q000502:physiology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000494:pharmacology
D000199:Actins; D009842:Oligopeptides; D011135:Polysaccharides, Bacterial; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; C050671:capsular polysaccharide K12; C109968:seryl-leucyl-isoleucyl--glycyl-lysyl-valine; C099570:seryl-leucyl-isoleucyl-glycyl-arginyl-leucine; D000185:Actinin; D012697:Serine Endopeptidases; D014357:Trypsin