Proteinase-activated receptor-2 in human skin: tissue distribution and activation of keratinocytes by mast cell tryptase.

  • Steinhoff M
  • Corvera C
  • Thoma M
 et al. 
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Proteinase-activated receptor-2 (PAR-2) is a G-protein coupled receptor. Tryptic proteases cleave PAR-2 exposing a tethered ligand (SLIGKV), which binds and activates the receptor. Although PAR-2 is highly expressed by cultured keratinocytes and is an inflammatory mediator, its precise localization in the normal and inflamed human skin is unknown, and the proteases that activate PAR-2 in the skin have not been identified. We localized PAR-2 in human skin by immunohistochemistry, examined PAR-2 expression by RT-PCR and RNA blotting, and investigated PAR-2 activation by mast cell tryptase. PAR-2 was localized to keratinocytes, especially in the granular layer, to endothelial cells, hair follicles, myoepithelial cells of sweat glands, and dermal dendritic-like cells. PAR-2 was also highly expressed in keratinocytes and endothelial cells of inflamed skin. PAR-2 mRNA was detected in normal human skin by RT-PCR, and in cultured human keratinocytes and dermal microvascular endothelial cells by Northern hybridization. Trypsin, tryptase and a peptide corresponding to the tethered ligand (SLIGKVNH2) increased [Ca2+]i in keratinocytes, measured using Fura-2/AM. Although tryptase-containing mast cells were sparsely scattered in the normal dermis, they were numerous in the dermis in atopic dermatitis, and in the dermis, dermal-epidermal border, and occasionally within the lower epidermis in psoriasis. Tryptase may activate PAR-2 on keratinocytes and endothelial cells during inflammation.

Author-supplied keywords

  • Biological Transport
  • Biological Transport: physiology
  • Blotting, Northern
  • Calcium
  • Calcium: metabolism
  • Cells, Cultured
  • Chymases
  • Dermatitis, Atopic
  • Dermatitis, Atopic: enzymology
  • Dermatitis, Atopic: metabolism
  • Dermatitis, Atopic: pathology
  • Endothelium, Vascular
  • Endothelium, Vascular: metabolism
  • Endothelium, Vascular: pathology
  • Humans
  • Immunohistochemistry
  • Keratinocytes
  • Keratinocytes: physiology
  • Mast Cells
  • Mast Cells: enzymology
  • Microcirculation
  • Microcirculation: physiology
  • Receptor, PAR-2
  • Receptors, Thrombin
  • Receptors, Thrombin: metabolism
  • Receptors, Thrombin: physiology
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serine Endopeptidases
  • Serine Endopeptidases: metabolism
  • Serine Endopeptidases: physiology
  • Skin
  • Skin: blood supply
  • Skin: metabolism
  • Skin: pathology
  • Tissue Distribution
  • Tissue Distribution: physiology
  • Tryptases

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  • M Steinhoff

  • C U Corvera

  • M S Thoma

  • W Kong

  • B E McAlpine

  • G H Caughey

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