title: Decreased chymase activity is associated with increased levels of protease inhibitors in mast cells of psoriatic lesions.
abstract: Mast cells contain large amounts of the powerful serine proteinases, tryptase and chymase, of which only chymase can be inactivated by serum protease inhibitors. In this study, 20 patients with psoriasis and a control group of 13 with atopic dermatitis were biopsied for lesional and non-lesional skin specimens. The presence of chymase inhibitor alpha 1-proteinase inhibitor (alpha 1-PI), alpha 1-antichymotrypsin (alpha 1-AC), alpha 2-macroglobulin (alpha 2-MG) and C1-esterase inhibitor (C1-Inh) immunoreactivity in mast cells was verified using the sequential double-staining method. Tryptase- and chymase-positive mast cells were stained enzyme-histochemically. Tryptase-positive mast cells were increased in number in the upper dermis of the psoriatic lesion compared with lesion-free psoriatic skin (308 +/- 109 vs. 100 +/- 29 cells/mm2, respectively, mean +/- SD, p < 0.0005, t-test) while the percentage of mast cells showing chymase activity was decreased (76.8 +/- 22.1% vs. 28.6 +/- 14.4%, p < 0.0005). These findings are consistent with our previous ones. In contrast to the decreased percentage of chymase-positive mast cells, a novel finding was that the percentages of alpha 1-AC+ (86.9 +/- 7.2% vs. 59.5 +/- 12.6%, p < 0.0005), alpha 1-PI+ (72.2 +/- 14.9% vs. 33.4 +/- 18.6%, p < 0.0005) and alpha 2-MG+ (16.8 +/- 7.0% vs. 6.2 +/- 3.5%, p < 0.002) mast cells were significantly higher in the psoriatic lesion with the exception of the percentage of C1-Inh+ mast cells (13.7 +/- 10.0% vs. 11.0 +/- 6.1%, p < 0.7). The localization of these inhibitors in mast cells is not a characteristic feature of psoriasis, since mast cells in atopic dermatitis skin also showed immunoreactivity though in slightly lower percentages. Previously, we have shown that MCTC (tryptase+, chymase+) mast cells increase in number in the psoriatic lesion but chymase becomes inactive. The results of this study show again the decreased chymase activity, which could be due to increased levels of its inhibitors (alpha 1-AC, alpha 1-PI and alpha 2-MG) in the same mast cells. Thus, active tryptase could promote inflammation but chymase seems not to be an important mediator in the pathomechanism of psoriasis.
authors.affiliation: Department of Dermatology, Kuopio University Hospital, Finland. ilkka.harvima@kuh.fi
authors.forename: I T
authors.initials: IT
authors.lastname: Harvima
authors.forename: L
authors.initials: L
authors.lastname: Haapanen
authors.forename: L
authors.initials: L
authors.lastname: Ackermann
authors.forename: A
authors.initials: A
authors.lastname: Naukkarinen
authors.forename: R J
authors.initials: RJ
authors.lastname: Harvima
authors.forename: M
authors.initials: M
authors.lastname: Horsmanheimo
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D053818:Chymases; D003876:Dermatitis, Atopic / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008407:Mast Cells / Q000201:enzymology*; D008875:Middle Aged; D011480:Protease Inhibitors / Q000378:metabolism*; D011565:Psoriasis / Q000201:enzymology* / Q000473:pathology; D012697:Serine Endopeptidases / Q000378:metabolism*; D053802:Tryptases
chemical_list: D011480:Protease Inhibitors; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases